Amyloid Self-Assembly of hIAPP8-20 via the Accumulation of Helical Oligomers, α-Helix to β-Sheet Transition, and Formation of β-Barrel Intermediates.

ABSTRACT: The self-assembly of human islet amyloid polypeptide (hIAPP) into β-sheet-rich nanofibrils is associated with the pathogeny of type 2 diabetes. Soluble hIAPP is intrinsically disordered with N-terminal residues 8-17 as α-helices. To understand the contribution of the N-terminal helix to the aggregation of full-length hIAPP, here the oligomerization dynamics of the hIAPP fragment 8-20 (hIAPP8-20) are investigated with combined computational and experimental approaches. hIAPP8-20 forms cross-β nanofibrils in silico from isolated helical monomers via the helical oligomers and α-helices to β-sheets transition, as confirmed by transmission electron microscopy, atomic force microscopy, circular dichroism spectroscopy, Fourier transform infrared spectroscopy, and reversed-phase high performance l

SUBMITTER: Sun Y 

PROVIDER: S-EPMC6499678 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature