Quantitative NMR analysis of the mechanism and kinetics of chaperone Hsp104 action on amyloid-β42 aggregation and fibril formation.

ABSTRACT: The chaperone Hsp104, a member of the Hsp100/Clp family of translocases, prevents fibril formation of a variety of amyloidogenic peptides in a paradoxically substoichiometric manner. To understand the mechanism whereby Hsp104 inhibits fibril formation, we probed the interaction of Hsp104 with the Alzheimer's amyloid-β42 (Aβ42) peptide using a variety of biophysical techniques. Hsp104 is highly effective at suppressing the formation of Thioflavin T (ThT) reactive mature fibrils that are readily observed by atomic force (AFM) and electron (EM) microscopies. Quantitative kinetic analysis and global fitting was performed on serially recorded ¹H-¹⁵N correlation spectra to monitor the disappearance of Aβ42 monomers during the course of aggregation over a wide range of Hsp10

SUBMITTER: Ghosh S 

PROVIDER: S-EPMC10214214 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature