Amyloidogenesis Abolished by Proline Substitutions but Enhanced by Lipid Binding
作者： Ping Jiang , Weixin Xu , Yuguang Mu
DOI: 10.1371/JOURNAL.PCBI.1000357
关键词: Plasma protein binding 、 Molecule 、 Antiparallel (biochemistry) 、 Solvent 、 Hydrophobic effect 、 Binding site 、 Biophysics 、 Molecular dynamics 、 Proline 、 Chemistry 、 Biochemistry 、 Ecology (disciplines) 、 Modelling and Simulation 、 Computational Theory and Mathematics 、 Genetics 、 Ecology, Evolution, Behavior and Systematics 、 Molecular biology 、 Cellular and Molecular Neuroscience
摘要: The influence of lipid molecules on the aggregation a highly amyloidogenic segment human islet amyloid polypeptide, hIAPP20–29, and corresponding sequence from rat has been studied by all-atom replica exchange molecular dynamics (REMD) simulations with explicit solvent model. hIAPP20–29 fragments aggregate into partially ordered β-sheet oligomers then undergo large conformational reorganization convert parallel/antiparallel in mixed in-register out-of-register patterns. hydrophobic interaction between tails residues at positions 23–25 is found to stabilize structure, indicating catalysis role self-assembly. IAPP variants three proline maintain unstructured micelle-like oligomers, which consistent non-amyloidogenic behavior observed experimental studies. Our study provides atomic resolution descriptions catalytic function peptides.
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