Please use this identifier to cite or link to this item: 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
Rights: © 2012 The Authors.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

Files in This Item:
File Description SizeFormat 
18. Lipid Interaction and Membrane Perturbation.pdf756.13 kBAdobe PDFThumbnail
View/Open

SCOPUSTM   
Citations 10

33
Updated on Sep 1, 2020

PublonsTM
Citations 10

27
Updated on Mar 5, 2021

Page view(s) 20

473
Updated on May 6, 2021

Download(s) 20

259
Updated on May 6, 2021

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.