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https://hdl.handle.net/10356/95431
Title: | Lipid interaction and membrane perturbation of human islet amyloid polypeptide monomer and dimer by molecular dynamics simulations | Authors: | Zhang, Yun Luo, Yin Deng, Yonghua Mu, Yuguang Wei, Guanghong |
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 http://hdl.handle.net/10220/9294 |
ISSN: | 1932-6203 | DOI: | 10.1371/journal.pone.0038191 | Schools: | School of Biological Sciences | Rights: | © 2012 The Authors. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SBS Journal Articles |
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18. Lipid Interaction and Membrane Perturbation.pdf | 756.13 kB | Adobe PDF | View/Open |
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