Human islet amyloid polypeptide monomers form ordered beta-hairpins: a possible direct amyloidogenic precursor.

ABSTRACT: Oligomerization of human islet amyloid polypeptide (IAPP) has been increasingly considered a pathogenic process in type II diabetes. Here structural features of the IAPP monomer have been probed using a combination of ion mobility mass spectrometry (IMS-MS) and all-atom replica exchange molecular dynamics (REMD) simulations. Three distinct conformational families of human IAPP monomer are observed in IMS experiments, and two of them are identified as dehydrated solution structures on the basis of our simulation results: one is an extended beta-hairpin structural family, and the second is a compact helix-coil structural family. The extended beta-hairpin family is topologically similar to the peptide conformation in the solid-state NMR fibril structure published by Tycko and co-workers. It i

SUBMITTER: Dupuis NF 

PROVIDER: S-EPMC2810149 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature