7RAX

ATP-binding state of the nucleotide-binding domain of Hsp70 DnaK mutant T199A

7RAX の概要

• エントリーDOI: 10.2210/pdb7rax/pdb
• 分子名称: Chaperone protein DnaK, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (7 entities in total)
• 機能のキーワード: molecular chaperone, hsp70, protein folding, chaperone
• 由来する生物種: Escherichia coli (strain K12)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 43236.80

構造登録者

Wang, W.,Hendrickson, W.A. (登録日: 2021-07-04, 公開日: 2023-07-05, 最終更新日: 2024-10-09)

主引用文献

Wang, W.,Liu, Q.,Liu, Q.,Hendrickson, W.A.
Conformational equilibria in allosteric control of Hsp70 chaperones.
Mol.Cell, 81:3919-3933.e7, 2021

PubMed 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-ATP, restricts ATP hydrolysis and binds peptides poorly, whereas a stimulating state, Hsp70-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.

PubMed: 34453889
DOI: 10.1016/j.molcel.2021.07.039

実験手法

X-RAY DIFFRACTION (1.41 Å)