7n46

Publication Abstract from PubMed

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, Hsp70R-ATP, restricts ATP hydrolysis and binds peptides poorly, whereas a stimulating state, Hsp70S-ATP, hydrolyzes ATP rapidly and has high intrinsic substrate affinity but rapid binding kinetics. We support this model for allosteric regulation with DnaK structures obtained in the postulated stimulating state S with biochemical tests of the S-state interface and with improved peptide-binding-site definition in an R-state structure.

Conformational equilibria in allosteric control of Hsp70 chaperones.,Wang W, Liu Q, Liu Q, Hendrickson WA Mol Cell. 2021 Aug 26. pii: S1097-2765(21)00623-7. doi:, 10.1016/j.molcel.2021.07.039. PMID:34453889^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.