Mechanistic insights into the switch of ?B-crystallin chaperone activity and self-multimerization.

ABSTRACT: ?B-Crystallin (?Bc) is a small heat shock protein that protects cells against abnormal protein aggregation and disease-related degeneration. ?Bc is also a major structural protein that forms polydisperse multimers that maintain the liquid-like property of the eye lens. However, the relationship and regulation of the two functions have yet to be explored. Here, by combining NMR spectroscopy and multiple biophysical approaches, we found that ?Bc uses a conserved ?4/?8 surface of the central ?-crystallin domain to bind ?-synuclein and Tau proteins and prevent them from aggregating into pathological amyloids. We noted that this amyloid-binding surface can also bind the C-terminal IPI motif of ?Bc, which mediates ?Bc multimerization and weakens its chaperone activity. We further show that disruption of the IPI binding impairs ?Bc self-multimerization but enhances its chaperone activity. Our work discloses the structural mechanism underlying the regulation of ?Bc chaperone activity and self-multimerization and sheds light on the different functions of ?Bc in antagonizing neurodegeneration and maintaining eye lens liquidity.

SUBMITTER: Liu Z 

PROVIDER: S-EPMC6153274 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature