7L7I

Cryo-EM structure of Hsp90:FKBP51:p23 closed-state complex

7L7I の概要

• エントリーDOI: 10.2210/pdb7l7i/pdb
• 関連するPDBエントリー: 7L7J
• EMDBエントリー: 23213 23214
• 分子名称: Peptidyl-prolyl cis-trans isomerase FKBP5, Heat shock protein HSP 90-alpha, Prostaglandin E synthase 3, ... (4 entities in total)
• 機能のキーワード: isomerase-chaperone complex, isomerase/chaperone
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 240586.43

構造登録者

Lee, K.,Thwin, A.C.,Tse, E.,Gates, S.N.,Southworth, D.R. (登録日: 2020-12-28, 公開日: 2021-08-25, 最終更新日: 2024-05-29)

主引用文献

Lee, K.,Thwin, A.C.,Nadel, C.M.,Tse, E.,Gates, S.N.,Gestwicki, J.E.,Southworth, D.R.
The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state.
Mol.Cell, 81:3496-, 2021

PubMed Abstract: The Hsp90 chaperone promotes folding and activation of hundreds of client proteins in the cell through an ATP-dependent conformational cycle guided by distinct cochaperone regulators. The FKBP51 immunophilin binds Hsp90 with its tetratricopeptide repeat (TPR) domain and catalyzes peptidyl-prolyl isomerase (PPIase) activity during folding of kinases, nuclear receptors, and tau. Here we determined the cryoelectron microscopy (cryo-EM) structure of the human Hsp90:FKBP51:p23 complex to 3.3 Å, which, together with mutagenesis and crosslinking analyses, reveals the basis for cochaperone binding to Hsp90 during client maturation. A helix extension in the TPR functions as a key recognition element, interacting across the Hsp90 C-terminal dimer interface presented in the closed, ATP conformation. The PPIase domain is positioned along the middle domain, adjacent to Hsp90 client binding sites, whereas a single p23 makes stabilizing interactions with the N-terminal dimer. With this architecture, FKBP51 is positioned to act on specific client residues presented during Hsp90-catalyzed remodeling.

PubMed: 34380015
DOI: 10.1016/j.molcel.2021.07.023

実験手法

ELECTRON MICROSCOPY (3.3 Å)