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|Title:||Lipid interaction and membrane perturbation of human islet amyloid polypeptide monomer and dimer by molecular dynamics simulations||Authors:||Zhang, Yun
|Issue Date:||2012||Source:||Zhang, Y., Luo, Y., Deng, Y., Mu, Y., & Wei, G. (2012). Lipid Interaction and Membrane Perturbation of Human Islet Amyloid Polypeptide Monomer and Dimer by Molecular Dynamics Simulations. PLoS ONE, 7(5).||Series/Report no.:||PLoS oNE||Abstract:||The aggregation of human islet amyloid polypeptide (hIAPP or amylin) is associated with the pathogenesis of type 2 diabetes mellitus. Increasing evidence suggests that the interaction of hIAPP with β-cell membranes plays a crucial role in cytotoxicity. However, the hIAPP-lipid interaction and subsequent membrane perturbation is not well understood at atomic level. In this study, as a first step to gain insight into the mechanism of hIAPP-induced cytotoxicity, we have investigated the detailed interactions of hIAPP monomer and dimer with anionic palmitoyloleolyophosphatidylglycerol (POPG) bilayer using all-atom molecular dynamics (MD) simulations. Multiple MD simulations have been performed by employing the initial configurations where the N-terminal region of hIAPP is pre-inserted in POPG bilayer. Our simulations show that electrostatic interaction between hIAPP and POPG bilayer plays a major role in peptide-lipid interaction. In particular, the N-terminal positively-charged residues Lys1 and Arg11 make a dominant contribution to the interaction. During peptide-lipid interaction process, peptide dimerization occurs mostly through the C-terminal 20–37 region containing the amyloidogenic 20–29-residue segment. Membrane-bound hIAPP dimers display a pronounced ability of membrane perturbation than monomers. The higher bilayer perturbation propensity of hIAPP dimer likely results from the cooperativity of the peptide-peptide interaction (or peptide aggregation). This study provides insight into the hIAPP-membrane interaction and the molecular mechanism of membrane disruption by hIAPP oligomers.||URI:||https://hdl.handle.net/10356/95431
|ISSN:||1932-6203||DOI:||10.1371/journal.pone.0038191||Rights:||© 2012 The Authors.||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SBS Journal Articles|
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