7ZR0

CryoEM structure of HSP90-CDC37-BRAF(V600E) complex.

7ZR0 の概要

• エントリーDOI: 10.2210/pdb7zr0/pdb
• EMDBエントリー: 14875
• 分子名称: Heat shock protein HSP 90-beta, Hsp90 co-chaperone Cdc37, Serine/threonine-protein kinase B-raf, ... (4 entities in total)
• 機能のキーワード: complex, protein binding, 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: 311249.62

構造登録者

Oberoi, J.,Pearl, L.H. (登録日: 2022-05-03, 公開日: 2022-12-14, 最終更新日: 2025-07-09)

主引用文献

Oberoi, J.,Guiu, X.A.,Outwin, E.A.,Schellenberger, P.,Roumeliotis, T.I.,Choudhary, J.S.,Pearl, L.H.
HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation.
Nat Commun, 13:7343-7343, 2022

PubMed Abstract: Activation of client protein kinases by the HSP90 molecular chaperone system is affected by phosphorylation at multiple sites on HSP90, the kinase-specific co-chaperone CDC37, and the kinase client itself. Removal of regulatory phosphorylation from client kinases and their release from the HSP90-CDC37 system depends on the Ser/Thr phosphatase PP5, which associates with HSP90 via its N-terminal TPR domain. Here, we present the cryoEM structure of the oncogenic protein kinase client BRAF bound to HSP90-CDC37, showing how the V600E mutation favours BRAF association with HSP90-CDC37. Structures of HSP90-CDC37-BRAF complexes with PP5 in autoinhibited and activated conformations, together with proteomic analysis of its phosphatase activity on BRAF and CRAF, reveal how PP5 is activated by recruitment to HSP90 complexes. PP5 comprehensively dephosphorylates client proteins, removing interaction sites for regulatory partners such as 14-3-3 proteins and thus performing a 'factory reset' of the kinase prior to release.

PubMed: 36446791
DOI: 10.1038/s41467-022-35143-2

実験手法

ELECTRON MICROSCOPY (3.4 Å)