8FX4

GC-C-Hsp90-Cdc37 regulatory complex

Summary for 8FX4

• Entry DOI: 10.2210/pdb8fx4/pdb
• EMDB information: 29523
• Descriptor: Heat shock protein HSP 90-beta, Hsp90 co-chaperone Cdc37, Guanylyl cyclase C, ... (4 entities in total)
• Functional Keywords: guanylyl cyclase, receptor, heat shock protein, regulation, signaling protein, signaling protein-chaperone complex, signaling protein/chaperone
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 298313.02

Authors

Caveney, N.A.,Garcia, K.C. (deposition date: 2023-01-23, release date: 2023-07-12, Last modification date: 2025-06-04)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.9 Å)