Quantitative NMR Study of Insulin-Degrading Enzyme Using Amyloid-β and HIV-1 p6 Elucidates Its Chaperone Activity.

ABSTRACT: Insulin-degrading enzyme (IDE) hydrolyzes monomeric polypeptides, including amyloid-β (Aβ) and HIV-1 p6. It also acts as a nonproteolytic chaperone to prevent Aβ polymerization. Here we compare interactions of Aβ and non-amyloidogenic p6 with IDE. Although both exhibited similar proteolysis rates, the binding kinetics to an inactive IDE characterized using relaxation-based NMR were remarkably different. IDE and Aβ formed a sparsely populated complex with a lifetime of milliseconds in which a short hydrophobic cleavage segment of Aβ was anchored to IDE. Strikingly, a second and more stable complex was significantly populated with a subsecond lifetime owing to multiple intermolecular contacts between Aβ and IDE. By selectively sequestering Aβ in this nonproductive complex, IDE likely increas

SUBMITTER: Ramaraju B 

PROVIDER: S-EPMC8895387 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature