Conformations of islet amyloid polypeptide monomers in a membrane environment: implications for fibril formation.

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 hu

SUBMITTER: Duan M 

PROVIDER: S-EPMC3487734 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature