Conformational equilibria in allosteric control of Hsp70 chaperones.

ABSTRACT: Heat-shock proteins of 70 kDa (Hsp70s) are vital for all life and are notably important in protein folding. Hsp70s use ATP binding and hydrolysis at a nucleotide-binding domain (NBD) to control the binding and release of client polypeptides at a substrate-binding domain (SBD); however, the mechanistic basis for this allostery has been elusive. Here, we first characterize biochemical properties of selected domain-interface mutants in bacterial Hsp70 DnaK. We then develop a theoretical model for allosteric equilibria among Hsp70 conformational states to explain the observations: a restraining state, Hsp70_R-ATP, restricts ATP hydrolysis and binds peptides poorly, whereas a stimulating state, Hsp70_S-ATP, hydrolyzes ATP rapidly and has high intrinsic substrate affinity but

SUBMITTER: Wang W 

PROVIDER: S-EPMC8500941 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature