Nucleation of β-rich oligomers and β-barrels in the early aggregation of human islet amyloid polypeptide.

ABSTRACT: The self-assembly of human islet amyloid polypeptide (hIAPP) into β-sheet rich amyloid aggregates is associated with pancreatic β-cell death in type 2 diabetes (T2D). Prior experimental studies of hIAPP aggregation reported the early accumulation of α-helical intermediates before the rapid conversion into β-sheet rich amyloid fibrils, as also corroborated by our experimental characterizations with transmission electron microscopy and Fourier transform infrared spectroscopy. Although increasing evidence suggests that small oligomers populating early hIAPP aggregation play crucial roles in cytotoxicity, structures of these oligomer intermediates and their conformational conversions remain unknown, hindering our understanding of T2D disease mechanism and therapeutic design targeting these ear

SUBMITTER: Sun Y 

PROVIDER: S-EPMC6310638 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature