8FX4

GC-C-Hsp90-Cdc37 regulatory complex

8FX4 の概要

• エントリーDOI: 10.2210/pdb8fx4/pdb
• EMDBエントリー: 29523
• 分子名称: Heat shock protein HSP 90-beta, Hsp90 co-chaperone Cdc37, Guanylyl cyclase C, ... (4 entities in total)
• 機能のキーワード: guanylyl cyclase, receptor, heat shock protein, regulation, signaling protein, signaling protein-chaperone complex, signaling protein/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: 298313.02

構造登録者

Caveney, N.A.,Garcia, K.C. (登録日: 2023-01-23, 公開日: 2023-07-12, 最終更新日: 2025-06-04)

主引用文献

Caveney, N.A.,Tsutsumi, N.,Garcia, K.C.
Structural insight into guanylyl cyclase receptor hijacking of the kinase-Hsp90 regulatory mechanism.
Elife, 12:-, 2023

PubMed Abstract: Membrane receptor guanylyl cyclases play a role in many important facets of human physiology, from regulating blood pressure to intestinal fluid secretion. The structural mechanisms which influence these important physiological processes have yet to be explored. We present the 3.9 Å resolution cryo-EM structure of the human membrane receptor guanylyl cyclase GC-C in complex with Hsp90 and its co-chaperone Cdc37, providing insight into the mechanism of Cdc37 mediated binding of GC-C to the Hsp90 regulatory complex. As a membrane protein and non-kinase client of Hsp90-Cdc37, this work shows the remarkable plasticity of Cdc37 to interact with a broad array of clients with significant sequence variation. Furthermore, this work shows how membrane receptor guanylyl cyclases hijack the regulatory mechanisms used for active kinases to facilitate their regulation. Given the known druggability of Hsp90, these insights can guide the further development of membrane receptor guanylyl cyclase-targeted therapeutics and lead to new avenues to treat hypertension, inflammatory bowel disease, and other membrane receptor guanylyl cyclase-related conditions.

PubMed: 37535399
DOI: 10.7554/eLife.86784

実験手法

ELECTRON MICROSCOPY (3.9 Å)