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Publisher: Elsevier   (Total: 3184 journals)

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Showing 1 - 200 of 3184 Journals sorted alphabetically
Academic Pediatrics     Hybrid Journal   (Followers: 37, SJR: 1.655, CiteScore: 2)
Academic Radiology     Hybrid Journal   (Followers: 26, SJR: 1.015, CiteScore: 2)
Accident Analysis & Prevention     Partially Free   (Followers: 100, SJR: 1.462, CiteScore: 3)
Accounting Forum     Hybrid Journal   (Followers: 28, SJR: 0.932, CiteScore: 2)
Accounting, Organizations and Society     Hybrid Journal   (Followers: 40, SJR: 1.771, CiteScore: 3)
Achievements in the Life Sciences     Open Access   (Followers: 6)
Acta Anaesthesiologica Taiwanica     Open Access   (Followers: 7)
Acta Astronautica     Hybrid Journal   (Followers: 436, SJR: 0.758, CiteScore: 2)
Acta Automatica Sinica     Full-text available via subscription   (Followers: 2)
Acta Biomaterialia     Hybrid Journal   (Followers: 28, SJR: 1.967, CiteScore: 7)
Acta Colombiana de Cuidado Intensivo     Full-text available via subscription   (Followers: 3)
Acta de Investigación Psicológica     Open Access   (Followers: 3)
Acta Ecologica Sinica     Open Access   (Followers: 11, SJR: 0.18, CiteScore: 1)
Acta Histochemica     Hybrid Journal   (Followers: 3, SJR: 0.661, CiteScore: 2)
Acta Materialia     Hybrid Journal   (Followers: 307, SJR: 3.263, CiteScore: 6)
Acta Mathematica Scientia     Full-text available via subscription   (Followers: 5, SJR: 0.504, CiteScore: 1)
Acta Mechanica Solida Sinica     Full-text available via subscription   (Followers: 9, SJR: 0.542, CiteScore: 1)
Acta Oecologica     Hybrid Journal   (Followers: 12, SJR: 0.834, CiteScore: 2)
Acta Otorrinolaringologica (English Edition)     Full-text available via subscription  
Acta Otorrinolaringológica Española     Full-text available via subscription   (Followers: 2, SJR: 0.307, CiteScore: 0)
Acta Pharmaceutica Sinica B     Open Access   (Followers: 1, SJR: 1.793, CiteScore: 6)
Acta Poética     Open Access   (Followers: 4, SJR: 0.101, CiteScore: 0)
Acta Psychologica     Hybrid Journal   (Followers: 25, SJR: 1.331, CiteScore: 2)
Acta Sociológica     Open Access   (Followers: 1)
Acta Tropica     Hybrid Journal   (Followers: 6, SJR: 1.052, CiteScore: 2)
Acta Urológica Portuguesa     Open Access  
Actas Dermo-Sifiliograficas     Full-text available via subscription   (Followers: 3, SJR: 0.374, CiteScore: 1)
Actas Dermo-Sifiliográficas (English Edition)     Full-text available via subscription   (Followers: 2)
Actas Urológicas Españolas     Full-text available via subscription   (Followers: 3, SJR: 0.344, CiteScore: 1)
Actas Urológicas Españolas (English Edition)     Full-text available via subscription   (Followers: 1)
Actualites Pharmaceutiques     Full-text available via subscription   (Followers: 7, SJR: 0.19, CiteScore: 0)
Actualites Pharmaceutiques Hospitalieres     Full-text available via subscription   (Followers: 3)
Acupuncture and Related Therapies     Hybrid Journal   (Followers: 8)
Acute Pain     Full-text available via subscription   (Followers: 15, SJR: 2.671, CiteScore: 5)
Ad Hoc Networks     Hybrid Journal   (Followers: 11, SJR: 0.53, CiteScore: 4)
Addictive Behaviors     Hybrid Journal   (Followers: 18, SJR: 1.29, CiteScore: 3)
Addictive Behaviors Reports     Open Access   (Followers: 9, SJR: 0.755, CiteScore: 2)
Additive Manufacturing     Hybrid Journal   (Followers: 11, SJR: 2.611, CiteScore: 8)
Additives for Polymers     Full-text available via subscription   (Followers: 23)
Advanced Drug Delivery Reviews     Hybrid Journal   (Followers: 183, SJR: 4.09, CiteScore: 13)
Advanced Engineering Informatics     Hybrid Journal   (Followers: 12, SJR: 1.167, CiteScore: 4)
Advanced Powder Technology     Hybrid Journal   (Followers: 17, SJR: 0.694, CiteScore: 3)
Advances in Accounting     Hybrid Journal   (Followers: 9, SJR: 0.277, CiteScore: 1)
Advances in Agronomy     Full-text available via subscription   (Followers: 17, SJR: 2.384, CiteScore: 5)
Advances in Anesthesia     Full-text available via subscription   (Followers: 29, SJR: 0.126, CiteScore: 0)
Advances in Antiviral Drug Design     Full-text available via subscription   (Followers: 2)
Advances in Applied Mathematics     Full-text available via subscription   (Followers: 11, SJR: 0.992, CiteScore: 1)
Advances in Applied Mechanics     Full-text available via subscription   (Followers: 11, SJR: 1.551, CiteScore: 4)
Advances in Applied Microbiology     Full-text available via subscription   (Followers: 24, SJR: 2.089, CiteScore: 5)
Advances In Atomic, Molecular, and Optical Physics     Full-text available via subscription   (Followers: 15, SJR: 0.572, CiteScore: 2)
Advances in Biological Regulation     Hybrid Journal   (Followers: 4, SJR: 2.61, CiteScore: 7)
Advances in Botanical Research     Full-text available via subscription   (Followers: 2, SJR: 0.686, CiteScore: 2)
Advances in Cancer Research     Full-text available via subscription   (Followers: 33, SJR: 3.043, CiteScore: 6)
Advances in Carbohydrate Chemistry and Biochemistry     Full-text available via subscription   (Followers: 9, SJR: 1.453, CiteScore: 2)
Advances in Catalysis     Full-text available via subscription   (Followers: 5, SJR: 1.992, CiteScore: 5)
Advances in Cell Aging and Gerontology     Full-text available via subscription   (Followers: 5)
Advances in Cellular and Molecular Biology of Membranes and Organelles     Full-text available via subscription   (Followers: 14)
Advances in Chemical Engineering     Full-text available via subscription   (Followers: 29, SJR: 0.156, CiteScore: 1)
Advances in Child Development and Behavior     Full-text available via subscription   (Followers: 10, SJR: 0.713, CiteScore: 1)
Advances in Chronic Kidney Disease     Full-text available via subscription   (Followers: 10, SJR: 1.316, CiteScore: 2)
Advances in Clinical Chemistry     Full-text available via subscription   (Followers: 26, SJR: 1.562, CiteScore: 3)
Advances in Colloid and Interface Science     Full-text available via subscription   (Followers: 20, SJR: 1.977, CiteScore: 8)
Advances in Computers     Full-text available via subscription   (Followers: 14, SJR: 0.205, CiteScore: 1)
Advances in Dermatology     Full-text available via subscription   (Followers: 15)
Advances in Developmental Biology     Full-text available via subscription   (Followers: 13)
Advances in Digestive Medicine     Open Access   (Followers: 12)
Advances in DNA Sequence-Specific Agents     Full-text available via subscription   (Followers: 7)
Advances in Drug Research     Full-text available via subscription   (Followers: 26)
Advances in Ecological Research     Full-text available via subscription   (Followers: 43, SJR: 2.524, CiteScore: 4)
Advances in Engineering Software     Hybrid Journal   (Followers: 29, SJR: 1.159, CiteScore: 4)
Advances in Experimental Biology     Full-text available via subscription   (Followers: 8)
Advances in Experimental Social Psychology     Full-text available via subscription   (Followers: 51, SJR: 5.39, CiteScore: 8)
Advances in Exploration Geophysics     Full-text available via subscription   (Followers: 1)
Advances in Fluorine Science     Full-text available via subscription   (Followers: 9)
Advances in Food and Nutrition Research     Full-text available via subscription   (Followers: 65, SJR: 0.591, CiteScore: 2)
Advances in Fuel Cells     Full-text available via subscription   (Followers: 17)
Advances in Genetics     Full-text available via subscription   (Followers: 21, SJR: 1.354, CiteScore: 4)
Advances in Genome Biology     Full-text available via subscription   (Followers: 10, SJR: 12.74, CiteScore: 13)
Advances in Geophysics     Full-text available via subscription   (Followers: 7, SJR: 1.193, CiteScore: 3)
Advances in Heat Transfer     Full-text available via subscription   (Followers: 26, SJR: 0.368, CiteScore: 1)
Advances in Heterocyclic Chemistry     Full-text available via subscription   (Followers: 11, SJR: 0.749, CiteScore: 3)
Advances in Human Factors/Ergonomics     Full-text available via subscription   (Followers: 24)
Advances in Imaging and Electron Physics     Full-text available via subscription   (Followers: 3, SJR: 0.193, CiteScore: 0)
Advances in Immunology     Full-text available via subscription   (Followers: 36, SJR: 4.433, CiteScore: 6)
Advances in Inorganic Chemistry     Full-text available via subscription   (Followers: 10, SJR: 1.163, CiteScore: 2)
Advances in Insect Physiology     Full-text available via subscription   (Followers: 2, SJR: 1.938, CiteScore: 3)
Advances in Integrative Medicine     Hybrid Journal   (Followers: 6, SJR: 0.176, CiteScore: 0)
Advances in Intl. Accounting     Full-text available via subscription   (Followers: 3)
Advances in Life Course Research     Hybrid Journal   (Followers: 9, SJR: 0.682, CiteScore: 2)
Advances in Lipobiology     Full-text available via subscription   (Followers: 1)
Advances in Magnetic and Optical Resonance     Full-text available via subscription   (Followers: 8)
Advances in Marine Biology     Full-text available via subscription   (Followers: 21, SJR: 0.88, CiteScore: 2)
Advances in Mathematics     Full-text available via subscription   (Followers: 12, SJR: 3.027, CiteScore: 2)
Advances in Medical Sciences     Hybrid Journal   (Followers: 8, SJR: 0.694, CiteScore: 2)
Advances in Medicinal Chemistry     Full-text available via subscription   (Followers: 6)
Advances in Microbial Physiology     Full-text available via subscription   (Followers: 5, SJR: 1.158, CiteScore: 3)
Advances in Molecular and Cell Biology     Full-text available via subscription   (Followers: 24)
Advances in Molecular and Cellular Endocrinology     Full-text available via subscription   (Followers: 8)
Advances in Molecular Toxicology     Full-text available via subscription   (Followers: 7, SJR: 0.182, CiteScore: 0)
Advances in Nanoporous Materials     Full-text available via subscription   (Followers: 5)
Advances in Oncobiology     Full-text available via subscription   (Followers: 2)
Advances in Organ Biology     Full-text available via subscription   (Followers: 2)
Advances in Organometallic Chemistry     Full-text available via subscription   (Followers: 18, SJR: 1.875, CiteScore: 4)
Advances in Parallel Computing     Full-text available via subscription   (Followers: 7, SJR: 0.174, CiteScore: 0)
Advances in Parasitology     Full-text available via subscription   (Followers: 5, SJR: 1.579, CiteScore: 4)
Advances in Pediatrics     Full-text available via subscription   (Followers: 27, SJR: 0.461, CiteScore: 1)
Advances in Pharmaceutical Sciences     Full-text available via subscription   (Followers: 18)
Advances in Pharmacology     Full-text available via subscription   (Followers: 17, SJR: 1.536, CiteScore: 3)
Advances in Physical Organic Chemistry     Full-text available via subscription   (Followers: 9, SJR: 0.574, CiteScore: 1)
Advances in Phytomedicine     Full-text available via subscription  
Advances in Planar Lipid Bilayers and Liposomes     Full-text available via subscription   (Followers: 3, SJR: 0.109, CiteScore: 1)
Advances in Plant Biochemistry and Molecular Biology     Full-text available via subscription   (Followers: 10)
Advances in Plant Pathology     Full-text available via subscription   (Followers: 6)
Advances in Porous Media     Full-text available via subscription   (Followers: 5)
Advances in Protein Chemistry     Full-text available via subscription   (Followers: 19)
Advances in Protein Chemistry and Structural Biology     Full-text available via subscription   (Followers: 20, SJR: 0.791, CiteScore: 2)
Advances in Psychology     Full-text available via subscription   (Followers: 66)
Advances in Quantum Chemistry     Full-text available via subscription   (Followers: 6, SJR: 0.371, CiteScore: 1)
Advances in Radiation Oncology     Open Access   (Followers: 1, SJR: 0.263, CiteScore: 1)
Advances in Small Animal Medicine and Surgery     Hybrid Journal   (Followers: 3, SJR: 0.101, CiteScore: 0)
Advances in Space Biology and Medicine     Full-text available via subscription   (Followers: 6)
Advances in Space Research     Full-text available via subscription   (Followers: 421, SJR: 0.569, CiteScore: 2)
Advances in Structural Biology     Full-text available via subscription   (Followers: 5)
Advances in Surgery     Full-text available via subscription   (Followers: 13, SJR: 0.555, CiteScore: 2)
Advances in the Study of Behavior     Full-text available via subscription   (Followers: 37, SJR: 2.208, CiteScore: 4)
Advances in Veterinary Medicine     Full-text available via subscription   (Followers: 20)
Advances in Veterinary Science and Comparative Medicine     Full-text available via subscription   (Followers: 15)
Advances in Virus Research     Full-text available via subscription   (Followers: 5, SJR: 2.262, CiteScore: 5)
Advances in Water Resources     Hybrid Journal   (Followers: 53, SJR: 1.551, CiteScore: 3)
Aeolian Research     Hybrid Journal   (Followers: 6, SJR: 1.117, CiteScore: 3)
Aerospace Science and Technology     Hybrid Journal   (Followers: 383, SJR: 0.796, CiteScore: 3)
AEU - Intl. J. of Electronics and Communications     Hybrid Journal   (Followers: 8, SJR: 0.42, CiteScore: 2)
African J. of Emergency Medicine     Open Access   (Followers: 6, SJR: 0.296, CiteScore: 0)
Ageing Research Reviews     Hybrid Journal   (Followers: 12, SJR: 3.671, CiteScore: 9)
Aggression and Violent Behavior     Hybrid Journal   (Followers: 475, SJR: 1.238, CiteScore: 3)
Agri Gene     Hybrid Journal   (Followers: 1, SJR: 0.13, CiteScore: 0)
Agricultural and Forest Meteorology     Hybrid Journal   (Followers: 18, SJR: 1.818, CiteScore: 5)
Agricultural Systems     Hybrid Journal   (Followers: 31, SJR: 1.156, CiteScore: 4)
Agricultural Water Management     Hybrid Journal   (Followers: 45, SJR: 1.272, CiteScore: 3)
Agriculture and Agricultural Science Procedia     Open Access   (Followers: 4)
Agriculture and Natural Resources     Open Access   (Followers: 3)
Agriculture, Ecosystems & Environment     Hybrid Journal   (Followers: 58, SJR: 1.747, CiteScore: 4)
Ain Shams Engineering J.     Open Access   (Followers: 5, SJR: 0.589, CiteScore: 3)
Air Medical J.     Hybrid Journal   (Followers: 7, SJR: 0.26, CiteScore: 0)
AKCE Intl. J. of Graphs and Combinatorics     Open Access   (SJR: 0.19, CiteScore: 0)
Alcohol     Hybrid Journal   (Followers: 12, SJR: 1.153, CiteScore: 3)
Alcoholism and Drug Addiction     Open Access   (Followers: 11)
Alergologia Polska : Polish J. of Allergology     Full-text available via subscription   (Followers: 1)
Alexandria Engineering J.     Open Access   (Followers: 2, SJR: 0.604, CiteScore: 3)
Alexandria J. of Medicine     Open Access   (Followers: 1, SJR: 0.191, CiteScore: 1)
Algal Research     Partially Free   (Followers: 11, SJR: 1.142, CiteScore: 4)
Alkaloids: Chemical and Biological Perspectives     Full-text available via subscription   (Followers: 2)
Allergologia et Immunopathologia     Full-text available via subscription   (Followers: 1, SJR: 0.504, CiteScore: 1)
Allergology Intl.     Open Access   (Followers: 5, SJR: 1.148, CiteScore: 2)
Alpha Omegan     Full-text available via subscription   (SJR: 3.521, CiteScore: 6)
ALTER - European J. of Disability Research / Revue Européenne de Recherche sur le Handicap     Full-text available via subscription   (Followers: 10, SJR: 0.201, CiteScore: 1)
Alzheimer's & Dementia     Hybrid Journal   (Followers: 54, SJR: 4.66, CiteScore: 10)
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring     Open Access   (Followers: 6, SJR: 1.796, CiteScore: 4)
Alzheimer's & Dementia: Translational Research & Clinical Interventions     Open Access   (Followers: 6, SJR: 1.108, CiteScore: 3)
Ambulatory Pediatrics     Hybrid Journal   (Followers: 5)
American Heart J.     Hybrid Journal   (Followers: 58, SJR: 3.267, CiteScore: 4)
American J. of Cardiology     Hybrid Journal   (Followers: 63, SJR: 1.93, CiteScore: 3)
American J. of Emergency Medicine     Hybrid Journal   (Followers: 46, SJR: 0.604, CiteScore: 1)
American J. of Geriatric Pharmacotherapy     Full-text available via subscription   (Followers: 12)
American J. of Geriatric Psychiatry     Hybrid Journal   (Followers: 14, SJR: 1.524, CiteScore: 3)
American J. of Human Genetics     Hybrid Journal   (Followers: 37, SJR: 7.45, CiteScore: 8)
American J. of Infection Control     Hybrid Journal   (Followers: 29, SJR: 1.062, CiteScore: 2)
American J. of Kidney Diseases     Hybrid Journal   (Followers: 36, SJR: 2.973, CiteScore: 4)
American J. of Medicine     Hybrid Journal   (Followers: 50)
American J. of Medicine Supplements     Full-text available via subscription   (Followers: 3, SJR: 1.967, CiteScore: 2)
American J. of Obstetrics and Gynecology     Hybrid Journal   (Followers: 248, SJR: 2.7, CiteScore: 4)
American J. of Ophthalmology     Hybrid Journal   (Followers: 66, SJR: 3.184, CiteScore: 4)
American J. of Ophthalmology Case Reports     Open Access   (Followers: 5, SJR: 0.265, CiteScore: 0)
American J. of Orthodontics and Dentofacial Orthopedics     Full-text available via subscription   (Followers: 6, SJR: 1.289, CiteScore: 1)
American J. of Otolaryngology     Hybrid Journal   (Followers: 25, SJR: 0.59, CiteScore: 1)
American J. of Pathology     Hybrid Journal   (Followers: 32, SJR: 2.139, CiteScore: 4)
American J. of Preventive Medicine     Hybrid Journal   (Followers: 28, SJR: 2.164, CiteScore: 4)
American J. of Surgery     Hybrid Journal   (Followers: 39, SJR: 1.141, CiteScore: 2)
American J. of the Medical Sciences     Hybrid Journal   (Followers: 12, SJR: 0.767, CiteScore: 1)
Ampersand : An Intl. J. of General and Applied Linguistics     Open Access   (Followers: 7)
Anaerobe     Hybrid Journal   (Followers: 4, SJR: 1.144, CiteScore: 3)
Anaesthesia & Intensive Care Medicine     Full-text available via subscription   (Followers: 66, SJR: 0.138, CiteScore: 0)
Anaesthesia Critical Care & Pain Medicine     Full-text available via subscription   (Followers: 24, SJR: 0.411, CiteScore: 1)
Anales de Cirugia Vascular     Full-text available via subscription   (Followers: 1)
Anales de Pediatría     Full-text available via subscription   (Followers: 3, SJR: 0.277, CiteScore: 0)
Anales de Pediatría (English Edition)     Full-text available via subscription  
Anales de Pediatría Continuada     Full-text available via subscription  
Analytic Methods in Accident Research     Hybrid Journal   (Followers: 5, SJR: 4.849, CiteScore: 10)
Analytica Chimica Acta     Hybrid Journal   (Followers: 44, SJR: 1.512, CiteScore: 5)
Analytica Chimica Acta : X     Open Access  
Analytical Biochemistry     Hybrid Journal   (Followers: 209, SJR: 0.633, CiteScore: 2)
Analytical Chemistry Research     Open Access   (Followers: 13, SJR: 0.411, CiteScore: 2)
Analytical Spectroscopy Library     Full-text available via subscription   (Followers: 14)
Anesthésie & Réanimation     Full-text available via subscription   (Followers: 2)
Anesthesiology Clinics     Full-text available via subscription   (Followers: 25, SJR: 0.683, CiteScore: 2)
Angiología     Full-text available via subscription   (SJR: 0.121, CiteScore: 0)
Angiologia e Cirurgia Vascular     Open Access   (Followers: 1, SJR: 0.111, CiteScore: 0)
Animal Behaviour     Hybrid Journal   (Followers: 218, SJR: 1.58, CiteScore: 3)
Animal Feed Science and Technology     Hybrid Journal   (Followers: 6, SJR: 0.937, CiteScore: 2)
Animal Reproduction Science     Hybrid Journal   (Followers: 7, SJR: 0.704, CiteScore: 2)

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Similar Journals
Journal Cover
Advances in Protein Chemistry and Structural Biology
Journal Prestige (SJR): 0.791
Citation Impact (citeScore): 2
Number of Followers: 20  
 
  Full-text available via subscription Subscription journal
ISSN (Online) 1876-1623
Published by Elsevier Homepage  [3184 journals]
  • Structure-function relationships in KDM7 histone demethylases
    • Abstract: Publication date: Available online 10 September 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Shobhit S. Chaturvedi, Rajeev Ramanan, Sodiq O. Waheed, Tatyana G. Karabencheva-Christova, Christo Z. Christov The demethylation of lysine residues of histone proteins is a key epigenetic mechanism in cells. The enzymes that catalyze these processes are called histone demethylases (KDMs). The largest family of KDMs is the Jumonji C (JmjC) domain-containing enzymes; these includes KDM2-7 subfamily of enzymes. The JmjC proteins are Fe(II) and 2-Oxoglutarate (2OG) - dependent dioxygenases that couple substrate oxidation to decarboxylation of 2OG to form succinate and CO2. The KDM7 subfamily of enzymes - PHF8 (KDM7B) and KIAA1718 (KDM7A) are human JmjC 2OG-dependent Nε-methyl lysine demethylases and are involved in demethylation of lysine residues in histones such as H3K27me2/1, H3K9me2/1 and H4K20me1. These enzymes are involved in multiple pathologic processes, including cancers and mental retardation. In this chapter, we present the current state of the art in the structural, biochemical and computational studies of KDM7 enzymes.
       
  • Cytotoxic species in amyloid-associated diseases: Oligomers or mature
           fibrils
    • Abstract: Publication date: Available online 7 August 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Mohammad Khursheed Siddiqi, Sadia Malik, Nabeela Majid, Parvez Alam, Rizwan Hasan Khan Amyloid diseases especially, Alzheimer's disease (AD), is characterized by an imbalance between the production and clearance of amyloid-β (Aβ) species. Amyloidogenic proteins or peptides can transform structurally from monomers into β-stranded fibrils via multiple oligomeric states. Among various amyloid species, structured oligomers are proposed to be more toxic than fibrils; however, the identification of amyloid oligomers has been challenging due to their heterogeneous and metastable nature. Multiple techniques have recently helped in better understanding of oligomer's assembly details and structural properties. Moreover, some progress on elucidating the mechanisms of oligomer-triggered toxicity has been made. Based on the collection of current findings, there is growing consensus that control of toxic amyloid oligomers could be a valid approach to regulate amyloid-associated toxicity, which could advance development of new diagnostics and therapeutics for amyloid-related diseases. In this review, we have described the recent scenario of amyloid diseases with a great deal of information about the recent understanding of oligomers' assembly, structural properties, and toxicity. Also comprehensive details have been provided to differentiate the degree of toxicity associated with prefibrillar aggregates.
       
  • Comparison of DNA and RNA substrate effects on TET2 structure
    • Abstract: Publication date: Available online 11 June 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Emmett M. Leddin, G. Andrés Cisneros Ten-eleven translocation (TET) enzymes can perform the stepwise oxidation of 5-methylcytosine (5mC) to 5-carboxylcytosine on both single-stranded (ss) and double-stranded (ds) DNA and RNA. It has been established that TET2 has a preference for ds DNA substrates, but it can catalyze the oxidation reaction on both ssDNA and RNA. The reasons for this substrate preference have been investigated for only a substrate 5mC ribonucleotide in a DNA strand, but not other nucleic acid configurations (Biochemistry 58 (2019) 411). We performed molecular dynamics simulations on TET2 with various ss and ds substrates in order to better understand the structural and dynamical reasons for TET2's preference to act on ds DNA. Our simulations show that substrates that have a ribonucleotide experience several disruptions in their overall backbone shape, hydrogen bonding character, and non–bonded interactions. These differences appear to lead to the instability of ribonucleotide in the active site, and provide further rational for TET2's experimental behavior.
       
  • Glutarate L-2-hydroxylase (CsiD/GlaH) is an archetype
           Fe(II)/2-oxoglutarate-dependent dioxygenase
    • Abstract: Publication date: Available online 10 June 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Caitlyn Q Herr, Lee Macomber, Efthalia Kalliri, Robert P. Hausinger The Escherichia coli gene initially named ygaT is located adjacent to lhgO, encoding L-2-hydroxyglutarate oxidase/dehydrogenase, and the gabDTP gene cluster, utilized for γ-aminobutyric acid (GABA) metabolism. Because this gene is transcribed specifically during periods of carbon starvation, it was renamed csiD for carbon starvation induced. The CsiD protein was structurally characterized and shown to possess a double-stranded ß-helix fold, characteristic of a large family of non-heme Fe(II)- and 2-oxoglutarate (2OG)-dependent oxygenases. Consistent with a role in producing the substrate for LhgO, CsiD was shown to be a glutarate L-2-hydroxylase. We review the kinetic and structural properties of glutarate L-2-hydroxylase from E. coli and other species, and we propose a catalytic mechanism for this archetype 2OG-dependent hydroxylase. Glutarate can be derived from l-lysine within the cell, with the gabDT genes exhibiting expanded reactivities beyond those known for GABA metabolism. The complete CsiD-containing pathway provides a means for the cell to obtain energy from the metabolism of l-lysine during periods of carbon starvation. To reflect the role of this protein in the cell, a renaming of csiD to glaH has been proposed.
       
  • Sleep deprivation, oxidative stress and inflammation
    • Abstract: Publication date: Available online 24 April 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Fatin Atrooz, Samina Salim Adequate sleep is essential for normal brain function, especially during early life developmental stages as postnatal brain maturation occurs during the critical period of childhood and adolescence. Therefore, sleep disturbance and/or deficit during this period can have detrimental consequences. Many epidemiological and clinical studies have linked early life sleep disturbance with occurrence of later life behavioral and cognitive impairments. Role of oxidative stress and inflammation has been implicated in sleep deprivation-related impairments. This review article presents a detailed description of the current state of the literature on the subject.
       
  • Nucleobindins and encoded peptides: From cell signaling to physiology
    • Abstract: Publication date: Available online 17 April 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Adelaine Kwun-Wai Leung, Naresh Ramesh, Christine Vogel, Suraj Unniappan Nucleobindins (NUCBs) are DNA and calcium binding, secreted proteins with various signaling functions. Two NUCBs, nucleobindin-1 (NUCB1) and nucleobindin-2 (NUCB2), were discovered during the 1990s. These two peptides are shown to have diverse functions, including the regulation of inflammation and bone formation, among others. In 2006, Oh-I and colleagues discovered that three peptides encoded within the NUCB2 could be processed by prohormone convertases. These peptides were named nesfatin-1, 2 and 3, mainly due to the satiety and fat influencing properties of nesfatin-1. However, it was found that nesfatin-2 and -3 have no such effects. Nesfatin-1, especially its mid-segment, is very highly conserved across vertebrates. Although the receptor(s) that mediate nesfatin-1 effects are currently unknown, it is now considered an endogenous peptide with multiple functions, affecting central and peripheral tissues to regulate metabolism, reproduction, endocrine and other functions. We recently identified a nesfatin-1-like peptide (NLP) encoded within the NUCB1. Like nesfatin-1, NLP suppressed feed intake in mice and fish, and stimulated insulin secretion from pancreatic beta cells. There is considerable evidence available to indicate that nucleobindins and its encoded peptides are multifunctional regulators of cell biology and whole animal physiology. This review aims to briefly discuss the structure, distribution, functions and mechanism of action nucleobindins and encoded peptides.
       
  • Voices from the dead: The complex vocabulary and intricate grammar of dead
           cells
    • Abstract: Publication date: Available online 16 April 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Jerrold S. Levine, David S. Ucker Of the roughly one million cells per second dying throughout the body, the vast majority dies by apoptosis, the predominant form of regulated cell death in higher organisms. Long regarded as mere waste, apoptotic cells are now recognized as playing a prominent and active role in homeostatic maintenance, especially resolution of inflammation, and in the sculpting of tissues during development. The activities associated with apoptotic cells are continually expanding, with more recent studies demonstrating their ability to modulate such vital functions as proliferation, survival, differentiation, metabolism, migration, and angiogenesis. In each case, the role of apoptotic cells is active, exerting their effects via new activities acquired during the apoptotic program. Moreover, the capacity to recognize and respond to apoptotic cells is not limited to professional phagocytes. Most, if not all, cells receive and integrate an array of signals from cells dying in their vicinity. These signals comprise a form of biochemical communication. As reviewed in this chapter, this communication is remarkably sophisticated; each of its three critical steps—encoding, transmission, and decoding of the apoptotic cell's “message”—is endowed with exquisite robustness. Together, the abundance and intricacy of the variables at each step comprise the vocabulary and grammar of the language by which dead cells achieve their post-mortem voice. The combinatorial complexity of the resulting communication network permits dying cells, through the signals they emit and the responses those signals elicit, to partake of an expanded role in homeostasis, acting as both sentinels of environmental change and agents of adaptation.
       
  • From traveler to homebody: Which signaling mechanisms sponge larvae use to
           become adult sponges'
    • Abstract: Publication date: Available online 14 March 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Ilya Borisenko, Olga I. Podgornaya, Alexander V. Ereskovsky Cell-to-cell signaling is responsible for regulation of many developmental processes such as proliferation, cell migration, survival, cell fate specification and axis patterning. In this article we discussed the role of signaling in the metamorphosis of sponges with a focus on epithelial–mesenchymal transition (EMT) accompanying this event. Sponges (Porifera) are an ancient lineage of morphologically simple animals occupying a basal position on the tree of life. The study of these animals is necessary for understanding the origin of multicellularity and the evolution of developmental processes. Development of sponges is quite diverse. It finishes with the metamorphosis of a free-swimming larva into a young settled sponge. The outer surface of sponge larvae consists of a ciliated epithelial sheath, which ensures locomotion, while their internal structure varies from genus to genus. The fate of larval ciliated cells is the most intriguing aspect of metamorphosis. In this review we discuss the fate of larval ciliated cells, the processes going on in cells during metamorphosis at the molecular level and the regulation of this process. The review is based on information about several sponge species with a focus on Halisarca dujardini, Sycon ciliatum and Amphimedon queenslandica. In our model sponge, H. dujardini, ciliated cells leave the larval epithelium during metamorphosis and migrate to the internal cell mass as amoeboid cells to be differentiated into choanocytes of the juvenile sponge. Ciliated cells undergo EMT and internalize within minutes. As EMT involves the disappearance of adherens junctions and as cadherin, the main adherens junction protein, was identified in the transcriptome of several sponges, we suppose that EMT is regulated through cadherin-containing adherens junctions between ciliated cells. We failed to identify the master genes of EMT in the H. dujardini transcriptome, possibly because transcription was absent in the sequenced stages. They may be revealed by a search in the genome. The master genes themselves are controlled by various signaling pathways. Sponges have all the six signaling pathways conserved in Metazoa: Wnt, TGF-beta, Hedgehog, Notch, FGF and NO-dependent pathways. Summarizing the new data about intercellular communication in sponges, we can put forward two main questions regarding metamorphosis: (1) Which of the signaling pathways and in what hierarchical order are involved in metamorphosis' (2) How is the organization of a young sponge related to that of the larva or, in other words, is there a heredity of axes between the larva and the adult sponge'
       
  • Biological functions and clinical implications of interleukin-34 in
           inflammatory diseases
    • Abstract: Publication date: Available online 8 March 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Yun Ge, Man Huang, Xiao-mei Zhu, Yong-ming Yao Interleukin (IL)-34 is a recently discovered cytokine and ligand of the colony-stimulating factor (CSF)-1 receptor. Although CSF-1 and IL-34 share similar biological properties, their expression patterns and downstream signaling pathways are distinct. IL-34 can influence differentiation and has functions in multiple cell types (e.g., dendritic cells, monocytes, macrophages). In the pathological conditions, IL-34 is induced by pro-inflammatory stimuli (e.g., cytokines, pathogen-associated molecular patterns, and infection). Current evidence shows that IL-34 is a critical player in inflammatory response and is involved in the pathogenesis of inflammatory autoimmune dysfunction. Therefore, IL-34 may be a promising clinical biomarker and therapeutic target for treating inflammatory related disorders. In this article, we review the advances in biological functions of IL-34 and our understanding of its role in the development of inflammatory diseases as well as therapeutic applications.
       
  • Dopamine signaling in the striatum
    • Abstract: Publication date: Available online 22 February 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Emmanuel Valjent, Anne Biever, Giuseppe Gangarossa, Emma Puighermanal The striatum integrates dopamine-mediated reward signals to generate appropriate behavior in response to glutamate-mediated sensory cues. Such associative learning relies on enduring neural plasticity in striatal GABAergic spiny projection neurons which, when altered, can lead to the development of a wide variety of pathological states. Considerable progress has been made in our understanding of the intracellular signaling mechanisms in dopamine-related behaviors and pathologies. Through the prism of the regulation of histone H3 and ribosomal protein S6 phosphorylation, we review how dopamine-mediated signaling events regulate gene transcription and mRNA translation. Particularly, we focus on the intracellular cascades controlling these phosphorylations downstream of the modulation of dopamine receptors by psychostimulants, antipsychotics and l-DOPA. Finally, we highlight the importance to precisely determine in which neuronal populations these signaling events occur in order to understand how they participate in remodeling neural circuits and altering dopamine-related behaviors.
       
  • TFIIH: A multi-subunit complex at the cross-roads of transcription and DNA
           repair
    • Abstract: Publication date: Available online 10 February 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Olga Kolesnikova, Laura Radu, Arnaud Poterszman Transcription factor IIH (TFIIH) is a multiprotein complex involved in both eukaryotic transcription and DNA repair, revealing a tight connection between these two processes. Composed of 10 subunits, it can be resolved into a 7-subunits core complex with the XPB translocase and the XPD helicase, and the 3-subunits kinase complex CAK, which also exists as a free complex with a distinct function. Initially identified as basal transcription factor, TFIIH also participates in transcription regulation and plays a key role in nucleotide excision repair (NER) for opening DNA at damaged sites, lesion verification and recruitment of additional repair factors. Our understanding of TFIIH function in eukaryotic cells has greatly benefited from studies of the genetic rare diseases xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD), that are not only characterized by cancer and aging predispositions but also by neurological and developmental defects. Although much remains unknown about TFIIH function, significant progresses have been done regarding the structure of the complex, the functions of its catalytic subunits and the multiple roles of the regulatory core-TFIIH subunits. This review provides a non-exhaustive survey of key discoveries on the structure and function of this pivotal factor, which can be considered as a promising target for therapeutic strategies.
       
  • Estrogen receptor signaling mechanisms
    • Abstract: Publication date: Available online 4 February 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Nathalie Fuentes, Patricia Silveyra The primary female sex hormones, estrogens, are responsible for the control of functions of the female reproductive system, as well as the development of secondary sexual characteristics that appear during puberty and sexual maturity. Estrogens exert their actions by binding to specific receptors, the estrogen receptors (ERs), which in turn activate transcriptional processes and/or signaling events that result in the control of gene expression. These actions can be mediated by direct binding of estrogen receptor complexes to specific sequences in gene promoters (genomic effects), or by mechanisms that do not involve direct binding to DNA (non-genomic effects). Whether acting via direct nuclear effects, indirect non-nuclear actions, or a combination of both, the effects of estrogens on gene expression are controlled by highly regulated complex mechanisms. In this chapter, we summarize the knowledge gained in the past 60 years since the discovery of the estrogen receptors on the mechanisms governing estrogen-mediated gene expression. We provide an overview of estrogen biosynthesis, and we describe the main mechanisms by which the female sex hormone controls gene transcription in different tissues and cell types. Specifically, we address the molecular events governing regulation of gene expression via the nuclear estrogen receptors (ERα, and ERβ) and the membrane estrogen receptor (GPER1). We also describe mechanisms of cross-talk between signaling cascades activated by both nuclear and membrane estrogen receptors. Finally, we discuss natural compounds that are able to target specific estrogen receptors and their implications for human health and medical therapeutics.
       
  • Molecular signaling in bone cells: Regulation of cell differentiation and
           survival
    • Abstract: Publication date: Available online 4 February 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Lilian I. Plotkin, Angela Bruzzaniti The achievement of proper bone mass and architecture, and their maintenance throughout life requires the concerted actions of osteoblasts, the bone forming cells, and osteoclasts, the bone resorbing cells. The differentiation and activity of osteoblasts and osteoclasts are regulated by molecules produced by matrix-embedded osteocytes, as well as by cross talk between osteoblasts and osteoclasts through secreted factors. In addition, it is likely that direct contact between osteoblast and osteoclast precursors, and the contact of these cells with osteocytes and cells in the bone marrow, also modulates bone cell differentiation and function. With the advancement of molecular and genetic tools, our comprehension of the intracellular signals activated in bone cells has evolved significantly, from early suggestions that osteoblasts and osteoclasts have common precursors and that osteocytes are inert cells in the bone matrix, to the very sophisticated understanding of a network of receptors, ligands, intracellular kinases/phosphatases, transcription factors, and cell-specific genes that are known today. These advances have allowed the design and FDA-approval of new therapies to preserve and increase bone mass and strength in a wide variety of pathological conditions, improving bone health from early childhood to the elderly. We have summarized here the current knowledge on selected intracellular signal pathways activated in osteoblasts, osteocytes, and osteoclasts.
       
  • Intracellular signaling of the AMP-activated protein kinase
    • Abstract: Publication date: Available online 14 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Miribane Dërmaku-Sopjani, Mentor Sopjani AMP-activated protein kinase (AMPK) is an essential cellular energy sensor that senses the cellular energy status and maintains cellular energy balance. The AMPK coordinates cellular and whole-body energy homeostasis through stimulating catabolic ATP-producing and suppressing anabolic ATP-consuming intracellular signaling pathways. AMPK induces autophagy and inhibits cell growth in response to starvation, a process that involves regulating certain intracellular signaling molecules. Recent advances demonstrated the AMPK to exert tumor suppressor activity realized through various signaling molecules by stimulating different cellular processes such as apoptosis, autophagy and cell growth and proliferation. AMPK can also be used to protect against metabolic syndrome. AMPK has previously been reported to be either directly or indirectly involved in the regulation of many different cellular transport proteins of high importance for cellular physiology and pathophysiology. Thus, AMPK provides a necessary link between cellular energy metabolism and cellular transport activities. A better understanding of the AMPK role in intracellular signaling under physiological and pathological conditions may represent a potential strategy for developing therapies for treating many different human diseases and disorders, in which AMPK plays a key role.
       
  • Elucidating the role of interacting residues of the MSH2-MSH6 complex in
           DNA repair mechanism: A computational approach
    • Abstract: Publication date: Available online 7 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): D. Thirumal Kumar, B. Susmita, E. Judith, J. Priyadharshini Christy, C. George Priya Doss, Hatem Zayed The DNA repair system is crucial to repair the error resulting in DNA replication. MSH2-MSH6 protein complex plays a significant role in maintaining the mismatch repair mechanism. Mutations in the interface between the two proteins compromise their function in the repair process. The present study aims to understand the impact of missense mutations in the interacting sites of the MSH2-MSH6 protein complex. MSH6 is unstable due to the disordered N-terminal domain. This is stabilized by the MSH2 hetero-dimerization. We used pathogenicity and stability predictors to identify the missense mutations that could be more pathogenic with the destabilizing property. The mutations W764C of MSH2, and L1201F and G1316E of MSH6 were predicted to be highly deleterious and destabilizing by all the in silico predictors. The dynamic motion of the native and mutant (W764C) MSH2-MSH6 protein complexes was further investigated using Molecular Dynamics Simulations of the GROMACS package. The Root Mean Square Deviation (RMSD), Radius of Gyration (Rg), and change in a number of intramolecular hydrogen bonds (H-bonds) were analyzed using the embedded packages of GROMACS. From the simulation studies, we observed higher deviation, lower protein compactness, and a decrease in the number of intramolecular hydrogen bonds in the mutant W764C MSH2-MSH6 protein complex. The observed results from the computational methods suggest the involvement of higher structural impact on the MSH2-MSH6 protein complex upon W764C mutation could affect the DNA repair mechanism.
       
  • A computational model to predict the structural and functional
           consequences of missense mutations in O6-methylguanine DNA
           methyltransferase
    • Abstract: Publication date: Available online 7 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): D. Thirumal Kumar, Enid Mendonca, J. Priyadharshini Christy, C. George Priya Doss, Hatem Zayed DNA repair mechanism is a process through which the cell repairs its damaged DNA. Although there are several mechanisms involved in the DNA repair mechanisms, the direct reversal method is the simplest and does not require a reference template, in which the guanine bases are often methylated, and the methyl guanine methyl transferase protein (MGMT) reverses them. The mutations occurring in the MGMT protein might result in dysfunction of such DNA repair mechanism. In this study, we attempted to evaluate the impact of six missense mutations (Y114E, Y114A, R128G, R128A, R128K, and C145A) at three active-site positions (Y114, C145, and R128) as this might hinder the DNA binding to the protein. These six mutations were subjected to pathogenicity, stability, and conservation analysis using online servers such as PredictSNP, iStable, and ConSurf, respectively. From the predictions, all the six mutations were almost predicted to be significant. Considering true positives, true negatives, false positives, and false negatives, three mutations (Y114E, R128G, and C145A) showed “loss of DNA repair activity,” and were analyzed further using molecular dynamics simulations (MDS) using GROMACS for 50 ns. MDS run showed that the C145A mutant demonstrated higher structural deviation, decreased compactness, and the binding patterns. The Y114E mutant showed almost a null effect from the structural analysis. Finally, the R128G mutant showed structural variations in between the C145A and Y114E mutations of MGMT protein. We believe that the observed findings in this computational approach might further pave a way of providing better treatment measures by understanding the DNA repair mechanisms.
       
  • Aquaporin water channels: New perspectives on the potential role in
           inflammation
    • Abstract: Publication date: Available online 5 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Margherita Sisto, Domenico Ribatti, Sabrina Lisi Aquaporins (AQPs) are a family of membrane water channel proteins that osmotically modulate water fluid homeostasis in several tissues; some of them also transport small solutes such as glycerol. At the cellular level, the AQPs regulate not only cell migration and transepithelial fluid transport across membranes, but also common events that are crucial for the inflammatory response. Emerging data reveal a new function of AQPs in the inflammatory process, as demonstrated by their dysregulation in a wide range of inflammatory diseases including edematous states, cancer, obesity, wound healing and several autoimmune diseases. This chapter summarizes the discoveries made so far about the structure and functions of the AQPs and provides updated information on the underlying mechanisms of AQPs in several human inflammatory diseases. The discovery of new functions for AQPs opens new vistas offering promise for the discovery of mechanisms and therapeutic opportunities in inflammatory disorders.
       
  • Mechanistic link between DNA damage sensing, repairing and signaling
           factors and immune signaling
    • Abstract: Publication date: Available online 3 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Shibani Mukherjee, Salim Abdisalaam, Souparno Bhattacharya, Kalayarasan Srinivasan, Debapriya Sinha, Aroumougame Asaithamby Previously, DNA damage sensing, repairing and signaling machineries were thought to mainly suppress genomic instability in response to genotoxic stress. Emerging evidence indicates a crosstalk between DNA repair machinery and the immune system. In this chapter, we attempt to decipher the molecular choreography of how factors, including ATM, BRCA1, DNA-PK, FANCA/D2, MRE11, MUS81, NBS1, RAD51 and TREX1, of multiple DNA metabolic processes are directly or indirectly involved in suppressing cytosolic DNA sensing pathway-mediated immune signaling. We provide systematic details showing how different DDR factors’ roles in modulating immune signaling are not direct, but are rather a consequence of their inherent ability to sense, repair and signal in response to DNA damage. Unexpectedly, most DDR factors negatively impact the immune system; that is, the immune system shows defective signaling if there are defects in DNA repair pathways. Thus, in addition to their known DNA repair and replication functions, DDR factors help prevent erroneous activation of immune signaling. A more precise understanding of the mechanisms by which different DDR factors function in immune signaling can be exploited to redirect the immune system for both preventing and treating autoimmunity, cellular senescence and cancer in humans.
       
  • Recent advances in computational studies of GPCR-G protein interactions
    • Abstract: Publication date: Available online 3 January 2019Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Jinan Wang, Yinglong Miao Protein-protein interactions are key in cellular signaling. G protein-coupled receptors (GPCRs), the largest superfamily of human membrane proteins, are able to transduce extracellular signals (e.g., hormones and neurotransmitters) to intracellular proteins, in particular the G proteins. Since GPCRs serve as primary targets of ~ 1/3 of currently marketed drugs, it is important to understand mechanisms of GPCR signaling in order to design selective and potent drug molecules. This chapter focuses on recent advances in computational studies of the GPCR-G protein interactions using bioinformatics, protein-protein docking and molecular dynamics simulation approaches.
       
  • Replication stress: Driver and therapeutic target in genomically instable
           cancers
    • Abstract: Publication date: Available online 28 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Pepijn M. Schoonen, Sergi Guerrero Llobet, Marcel A.T.M. van Vugt Genomically instable cancers are characterized by progressive loss and gain of chromosomal fragments, and the acquisition of complex genomic rearrangements. Such cancers, including triple-negative breast cancers and high-grade serous ovarian cancers, typically show aggressive behavior and lack actionable driver oncogenes. Increasingly, oncogene-induced replication stress or defective replication fork maintenance is considered an important driver of genomic instability. Paradoxically, while replication stress causes chromosomal instability and thereby promotes cancer development, it intrinsically poses a threat to cellular viability. Apparently, tumor cells harboring high levels of replication stress have evolved ways to cope with replication stress. As a consequence, therapeutic targeting of such compensatory mechanisms is likely to preferentially target cancers with high levels of replication stress and may prove useful in potentiating chemotherapeutic approaches that exert their effects by interfering with DNA replication. Here, we discuss how replication stress drives chromosomal instability, and the cell cycle-regulated mechanisms that cancer cells employ to deal with replication stress. Importantly, we discuss how mechanisms involving DNA structure-specific resolvases, cell cycle checkpoint kinases and mitotic processing of replication intermediates offer possibilities in developing treatments for difficult-to-treat genomically instable cancers.
       
  • Relationship between mitofusin 2 and cancer
    • Abstract: Publication date: Available online 27 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): A. Allegra, V. Innao, A.G. Allegra, C. Musolino Mitochondria are dynamic organelles whose actions are fundamental for cell viability. Within the cell, the mitochondrial system is incessantly modified via the balance between fusion and fission processes. Among other proteins, mitofusin 2 is a central protagonist in all these mitochondrial events (fusion, trafficking, contacts with other organelles), the balance of which causes the correct mitochondrial action, shape, and distribution within the cell. Here we examine the structural and functional characteristics of mitofusin 2, underlining its essential role in numerous intracellular pathways, as well as in the pathogenesis of cancer.
       
  • Activating mutations of the gp130/JAK/STAT pathway in human diseases
    • Abstract: Publication date: Available online 27 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Juliane Lokau, Christoph Garbers Cytokines of the interleukin-6 (IL-6) family are involved in numerous physiological and pathophysiological processes. Dysregulated and increased activities of its members can be found in practically all human inflammatory diseases including cancer. All cytokines activate several intracellular signaling cascades, including the Jak/STAT, MAPK, PI3K, and Src/YAP signaling pathways. Additionally, several mutations in proteins involved in these signaling cascades have been identified in human patients, which render these proteins constitutively active and result in a hyperactivation of the signaling pathway. Interestingly, some of these mutations are associated with or even causative for distinct human diseases, making them interesting targets for therapy. This chapter describes the basic biology of the gp130/Jak/STAT pathway, summarizes what is known about the molecular mechanisms of the activating mutations, and gives an outlook how this knowledge can be exploited for targeted therapy in human diseases.
       
  • DNA repair by photolyases
    • Abstract: Publication date: Available online 20 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Ibrahim Halil Kavakli, Nuri Ozturk, Seref Gul Photolyases belong to the cryptochrome/photolyase protein family (CPF) which perform different functions such as DNA repair, circadian photoreceptor, and transcriptional regulation. Photolyase is a flavoprotein that repairs UV-induced DNA damages of cyclobutane pyrimidine dimer (CPD) and pyrimidine-pyrimidone (6-4) photoproducts using blue-light as an energy source. This enzyme has two chromophores: flavin adenine dinucleotide (FAD) as a cofactor and a photoantenna such as methenyltetrahydrofolate (MTHF). The FAD is essential for catalysis of the DNA repair. The second chromophore absorbs photons from the blue light spectrum and transfers energy to FAD to increase the repair efficiency of the enzyme. Phylogenetic analysis in which amino acid sequences of several hundreds of CPF members are used suggests that they form more classes than we have considered so far. In this chapter, we discussed structure-functions and reaction mechanisms of different classes of photolyases.
       
  • Intracellular protein complexes involved in synapse assembly in
           presynaptic neurons
    • Abstract: Publication date: Available online 20 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Kyung Ah Han, Ji Won Um, Jaewon Ko The presynaptic active zone, composed of evolutionarily conserved protein complexes, is a specialized area that serves to orchestrate precise and efficient neurotransmitter release by organizing various presynaptic proteins involved in mediating docking and priming of synaptic vesicles, recruiting voltage-gated calcium channels, and modulating presynaptic nerve terminals with aligned postsynaptic structures. Among membrane proteins localized to active zone, presynaptic neurexins and LAR-RPTPs (leukocyte common antigen-related receptor tyrosine phosphatase) have emerged as hubs that orchestrate both shared and distinct extracellular synaptic adhesion pathways. In this chapter, we discuss intracellular signaling cascades involved in recruiting various intracellular proteins at both excitatory and inhibitory synaptic sites. In particular, we highlight recent studies on key active zone proteins that physically and functionally link these cascades with neurexins and LAR-RPTPs in both vertebrate and invertebrate model systems. These studies allow us to build a general, universal view of how presynaptic active zones operate together with postsynaptic structures in neural circuits.
       
  • Chromatin control in double strand break repair
    • Abstract: Publication date: Available online 20 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Anastas Gospodinov, Iva Ugrinova DNA double strand breaks (DSB) are the most deleterious type of damage inflicted on DNA by various environmental factors and as consequences of normal cellular metabolism. The multistep nature of DSB repair and the need to assemble large protein complexes at repair sites necessitate multiple chromatin changes there. This review focuses on the key findings of how chromatin regulators exert temporal and spatial control on DSB repair. These mechanisms coordinate repair with cell cycle progression, lead to DSB repair pathway choice, provide accessibility of repair machinery to damaged sites and move the lesions to nuclear environments permissive for repair.
       
  • Claspin: From replication stress and DNA damage responses to cancer
           therapy
    • Abstract: Publication date: Available online 5 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Diana Azenha, Maria Celeste Lopes, Teresa C. Martins Cancer is still one of the major causes of death worldwide. Radiation therapy and chemotherapy remain the main treatment modalities in cancer. These therapies exert their effect mainly through interference with DNA replication and induction of DNA damage. It is believed that one way of improving the efficacy of cancer treatment will be to inhibit the replication stress and DNA damage responses and promote mitotic catastrophe of cancer cells. So far, the majority of the efforts have focused central players of checkpoint responses, such as ATR and CHK1, and DNA damage repair, such as PARPs. Being a key player in the replication stress response, checkpoint activation, and the DNA damage response, Claspin constitutes an attractive therapeutic target in cancer, namely for radio- and chemo-sensitization. In this review, we will go through Claspin functions in the replication stress and DNA damage responses and will discuss how Claspin can be targeted in cancer treatment, as well as the effects of Claspin inhibition.
       
  • Controlling the balance between chromosome break repair pathways
    • Abstract: Publication date: Available online 5 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Sonia Jimeno, Fernando Mejías-Navarro, Rosario Prados-Carvajal, Pablo Huertas Broken chromosomes are among the most complex and more difficult to repair DNA lesions. The loss of the continuity of the DNA molecule presents a challenge to the cells, thus the repair of DNA double strand breaks might lead to genomic alterations. Indeed, to minimize this threat to genomic integrity, different DNA repair pathways can act on a broken chromosome. The balance between them is tightly controlled, and it heavily depends on global and local cellular cues. In this chapter, we review our current understanding on the repair of DNA double strand breaks and focus in the regulation of the balance between alternative pathways. Most of this modulation takes place at the level of DNA end resection. Here, we focus mostly on the local signals that control the repair pathway choice, as the global cues have been extensively reviewed recently. We described epigenetic marks that either facilitate or inhibit DNA resection and homologous recombination, from histone marks and chromatin remodelers to non-coding RNA and RNA-related factors.
       
  • cAMP-mediated regulation of melanocyte genomic instability: A
           melanoma-preventive strategy
    • Abstract: Publication date: Available online 5 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Nathaniel C. Holcomb, Robert-Marlo Bautista, Stuart G. Jarrett, Katharine M. Carter, Madeline Krentz Gober, John A. D’Orazio Malignant melanoma of the skin is the leading cause of death from skin cancer and ranks fifth in cancer incidence among all cancers in the United States. While melanoma mortality has remained steady for the past several decades, melanoma incidence has been increasing, particularly among fair-skinned individuals. According to the American Cancer Society, nearly 10,000 people in the United States will die from melanoma this year. Individuals with dark skin complexion are protected damage generated by UV-light due to the high content of UV-blocking melanin pigment in their epidermis as well as better capacity for melanocytes to cope with UV damage. There is now ample evidence that suggests that the melanocortin 1 receptor (MC1R) is a major melanoma risk factor. Inherited loss-of-function mutations in MC1R are common in melanoma-prone persons, correlating with a less melanized skin complexion and poorer recovery from mutagenic photodamage. We and others are interested in the MC1R signaling pathway in melanocytes, its mechanisms of enhancing genomic stability and pharmacologic opportunities to reduce melanoma risk based on those insights. In this chapter, we review melanoma risk factors, the MC1R signaling pathway, and the relationship between MC1R signaling and DNA repair.
       
  • Targeting DNA repair in precision medicine
    • Abstract: Publication date: Available online 5 December 2018Source: Advances in Protein Chemistry and Structural BiologyAuthor(s): Reena Beggs, Eddy S. Yang Precision medicine is an emerging treatment paradigm that aims to find the right therapy at the right time based on an individual's unique genetic background, environment, and lifestyle. One area of precision medicine that has had success is targeting DNA repair in cancer. DNA is exposed to constant stress and there are repair mechanisms in place to maintain genetic integrity. These repair mechanisms can be targeted as a treatment strategy. In this chapter, we will focus on current efforts to target DNA repair pathways as part of precision oncology-based treatments.
       
 
 
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