Effect of Post-Translational Amidation on Islet Amyloid Polypeptide Conformational Ensemble: Implications for Its Aggregation Early Steps.

ABSTRACT: The human islet amyloid polypeptide (hIAPP) is an intrinsically disordered protein that can self-assemble into fibrillar aggregates that play a key role in the pathogenesis of the type II diabetes mellitus. hIAPP can transiently adopt α -helix and β -strand conformations that could be important intermediate species on the fibrillization pathway. However, experimental studies of the monomeric peptide conformations are limited due to its high aggregation propensity, and the early steps of the hIAPP association are not clearly characterized. In particular, the question of whether the aggregation-prone conformation is α -helical or β -strand-rich is still debated. In this study, combining extensive all-atom molecular dynamics (MD) and replica exchange molecular dynamics (REMD) simulations in e

SUBMITTER: Tran L 

PROVIDER: S-EPMC5133895 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature