Celastrol regulates the oligomeric state and chaperone activity of αB-crystallin linked with protein homeostasis in the lens.

ABSTRACT: Protein misfolding and aggregation are crucial pathogenic factors for cataracts, which are the leading cause of visual impairment worldwide. α-crystallin, as a small molecular chaperone, is involved in preventing protein misfolding and maintaining lens transparency. The chaperone activity of α-crystallin depends on its oligomeric state. Our previous work identified a natural compound, celastrol, which could regulate the oligomeric state of αB-crystallin. In this work, based on the UNcle and SEC analysis, we found that celastrol induced αB-crystallin to form large oligomers. Large oligomer formation enhanced the chaperone activity of αB-crystallin and prevented aggregation of the cataract-causing mutant βA3-G91del. The interactions between αB-crystallin and celastrol were detected by the FR

SUBMITTER: Wang H 

PROVIDER: S-EPMC11197752 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature