8K2R

The structure of HtpG M domain in complex with unstructured D131D binding site b

8K2R の概要

• エントリーDOI: 10.2210/pdb8k2r/pdb
• 分子名称: Molecular chaperone HtpG (Fragment), Disordered protein(D131D) (2 entities in total)
• 機能のキーワード: e.coli hsp90, chaperone
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40148.50

構造登録者

Qu, X.,Huang, C. (登録日: 2023-07-13, 公開日: 2024-06-26, 最終更新日: 2024-10-30)

主引用文献

Qu, X.,Zhao, S.,Wan, C.,Zhu, L.,Ji, T.,Rossi, P.,Wang, J.,Kalodimos, C.G.,Wang, C.,Xu, W.,Huang, C.
Structural basis for the dynamic chaperoning of disordered clients by Hsp90.
Nat.Struct.Mol.Biol., 31:1482-1491, 2024

PubMed Abstract: Molecular chaperone heat shock protein 90 (Hsp90) is a ubiquitous regulator that fine-tunes and remodels diverse client proteins, exerting profound effects on normal biology and diseases. Unraveling the mechanistic details of Hsp90's function requires atomic-level insights into its client interactions throughout the adenosine triphosphate-coupled functional cycle. However, the structural details of the initial encounter complex in the chaperone cycle, wherein Hsp90 adopts an open conformation while engaging with the client, remain elusive. Here, using nuclear magnetic resonance spectroscopy, we determined the solution structure of Hsp90 in its open state, bound to a disordered client. Our findings reveal that Hsp90 uses two distinct binding sites, collaborating synergistically to capture discrete hydrophobic segments within client proteins. This bipartite interaction generates a versatile complex that facilitates rapid conformational sampling. Moreover, our investigations spanning various clients and Hsp90 orthologs demonstrate a pervasive mechanism used by Hsp90 orthologs to accommodate the vast array of client proteins. Collectively, our work contributes to establish a unified conceptual and mechanistic framework, elucidating the intricate interplay between Hsp90 and its clients.

PubMed: 38890550
DOI: 10.1038/s41594-024-01337-z

実験手法

SOLUTION NMR