C-Terminal Threonine Reduces Aβ43 Amyloidogenicity Compared with Aβ42.

ABSTRACT: Aβ43, a product of the proteolysis of the amyloid precursor protein APP, is related to Aβ42 by an additional Thr residue at the C-terminus. Aβ43 is typically generated at low levels compared with the predominant Aβ42 and Aβ40 forms, but it has been suggested that this longer peptide might have an impact on amyloid-β aggregation and Alzheimer's disease that is out of proportion to its brain content. Here, we report that both Aβ42 and Aβ43 spontaneously aggregate into mature amyloid fibrils via sequential appearance of the same series of oligomeric and protofibrillar intermediates, the earliest of which appears to lack β-structure. In spite of the additional β-branched amino acid at the C-terminus, Aβ43 fibrils have fewer strong backbone H-bonds than Aβ42 fibrils, some of which are lost at t

SUBMITTER: Chemuru S 

PROVIDER: S-EPMC4691432 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature