1BYQ

HSP90 N-TERMINAL DOMAIN BOUND TO ADP-MG

1BYQ の概要

• エントリーDOI: 10.2210/pdb1byq/pdb
• 分子名称: PROTEIN (HEAT SHOCK PROTEIN 90), MAGNESIUM ION, ADENOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: chaperone protein, atp binding, chaperone
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: P07900
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 26122.30

構造登録者

Russo, A.A.,Pavletich, N.P. (登録日: 1998-10-19, 公開日: 1998-10-28, 最終更新日: 2023-08-09)

主引用文献

Obermann, W.M.,Sondermann, H.,Russo, A.A.,Pavletich, N.P.,Hartl, F.U.
In vivo function of Hsp90 is dependent on ATP binding and ATP hydrolysis.
J.Cell Biol., 143:901-910, 1998

PubMed Abstract: Heat shock protein 90 (Hsp90), an abundant molecular chaperone in the eukaryotic cytosol, is involved in the folding of a set of cell regulatory proteins and in the re-folding of stress-denatured polypeptides. The basic mechanism of action of Hsp90 is not yet understood. In particular, it has been debated whether Hsp90 function is ATP dependent. A recent crystal structure of the NH2-terminal domain of yeast Hsp90 established the presence of a conserved nucleotide binding site that is identical with the binding site of geldanamycin, a specific inhibitor of Hsp90. The functional significance of nucleotide binding by Hsp90 has remained unclear. Here we present evidence for a slow but clearly detectable ATPase activity in purified Hsp90. Based on a new crystal structure of the NH2-terminal domain of human Hsp90 with bound ADP-Mg and on the structural homology of this domain with the ATPase domain of Escherichia coli DNA gyrase, the residues of Hsp90 critical in ATP binding (D93) and ATP hydrolysis (E47) were identified. The corresponding mutations were made in the yeast Hsp90 homologue, Hsp82, and tested for their ability to functionally replace wild-type Hsp82. Our results show that both ATP binding and hydrolysis are required for Hsp82 function in vivo. The mutant Hsp90 proteins tested are defective in the binding and ATP hydrolysis-dependent cycling of the co-chaperone p23, which is thought to regulate the binding and release of substrate polypeptide from Hsp90. Remarkably, the complete Hsp90 protein is required for ATPase activity and for the interaction with p23, suggesting an intricate allosteric communication between the domains of the Hsp90 dimer. Our results establish Hsp90 as an ATP-dependent chaperone.

PubMed: 9817749
DOI: 10.1083/jcb.143.4.901

実験手法

X-RAY DIFFRACTION (1.5 Å)