Conformations of Islet Amyloid Polypeptide Monomers in a Membrane Environment: Implications for Fibril Formation

Authors

Mojie Duan, Clark University
Jue Fan, Clark University
Shuanghong Huo, Clark UniversityFollow

Document Type

Article

Abstract

The amyloid fibrils formed by islet amyloid polypeptide (IAPP) are associated with type II diabetes. One of the proposed mechanisms of the toxicity of IAPP is that it causes membrane damage. The fatal mutation of S20G human IAPP was reported to lead to early onset of type II diabetes and high tendency of amyloid formation in vitro. Characterizing the structural features of the S20G mutant in its monomeric state is experimentally difficult because of its unusually fast aggregation rate. Computational work complements experimental studies. We performed a series of molecular dynamics simulations of the monomeric state of human variants in the membrane. Our simulations are validated by extensive comparisons with experimental data. We find that a helical disruption at His18 is common to both human variants. An L-shaped motif of S20G mutant is observed in one of the conformational families. This motif that bends at His18 resembles the overall topology of IAPP fibrils. The conformational preorganization into the fibril-like topology provides a possible explanation for the fast aggregation rate of S20G IAPP. © 2012 Duan et al.

Publication Title

PLoS ONE

Publication Date

11-2-2012

Volume

7

Issue

11

ISSN

1932-6203

DOI

10.1371/journal.pone.0047150

Keywords

membrane damage, molecular dynamics, protein aggregation, protein conformation, protein interaction, protein motif, simulation, structure analysis, wild type

Repository Citation

Duan, Mojie; Fan, Jue; and Huo, Shuanghong, "Conformations of Islet Amyloid Polypeptide Monomers in a Membrane Environment: Implications for Fibril Formation" (2012). Chemistry. 99.
https://commons.clarku.edu/chemistry/99

Cross Post Location

Student Publications

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright Conditions

Duan, M., Fan, J., & Huo, S. (2012). Conformations of islet amyloid polypeptide monomers in a membrane environment: implications for fibril formation. PloS one, 7(11), e47150.