Site-specific structural order in Alzheimer's Aβ42 fibrils.

ABSTRACT: Deposition of amyloid fibrils is a pathological hallmark of Alzheimer's disease. Aβ42 is the major protein whose aggregation leads to the formation of these fibrils. Understanding the detailed structure of Aβ42 fibrils is of particular importance for delineating the mechanism of Aβ42 aggregation and developing specific amyloid-targeting drugs. Here, we use site-directed spin labelling and electron paramagnetic resonance spectroscopy to study the site-specific structural order at each and every residue position in Aβ42 fibrils. Strong interactions between spin labels indicate highly ordered protein backbone at the labelling site, while weak interactions suggest disordered local structure. Our results show that Aβ42 consists of five β-strands (residues 2-7, 10-13, 17-20, 31-36, 39-41), three

SUBMITTER: Wang H 

PROVIDER: S-EPMC6083707 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature