9KDB

Structure of hTRPC3 in complex with Nb1-25 at 2.67 angstrom

This is a non-PDB format compatible entry.

Summary for 9KDB

• Entry DOI: 10.2210/pdb9kdb/pdb
• EMDB information: 62268
• Descriptor: Nb1-25, Short transient receptor potential channel 3, ZINC ION, ... (5 entities in total)
• Functional Keywords: trpc3, dag, nb1-25, nanobody, metal transport
• Biological source: Camelus; More
• Total number of polymer chains: 8
• Total formula weight: 507556.76

Authors

Chen, L.,Guo, W.,Chen, Y.,Zang, J. (deposition date: 2024-11-03, release date: 2025-10-08, Last modification date: 2025-11-12)

Primary citation

Chen, Y.,Zang, J.,Guo, W.,Xu, J.,Wei, M.,Quan, L.,Zhu, M.,Zhao, X.,Peng, H.,Wan, Y.,Chen, L.
Structural mechanism of the agonist binding on human TRPC3 channel.
Nat Commun, 16:9343-9343, 2025

PubMed Abstract: TRPC3/6/7 channels are cation channels that are directly activated by the second messenger diacylglycerol (DAG). These channels play crucial physiological roles and are implicated in various disease conditions; however, the binding mechanism of DAG to these channels remains incompletely understood. In this study, we present the structures of human TRPC3 in complex with DAG or synthetic activators, 4n and GSK1702934A. The structural analysis reveals that DAG binds at the L2 site, located near the pore on the extracellular side of TRPC3. Functional assays confirmed that the L2 site serves as the activating site for DAG. Notably, both 4n and GSK1702934A competitively bind to the same site, facilitating channel activation. Moreover, based on the pharmacophore identified from the DAG-bound structure, we found that monoacylglycerols (MAGs) are endogenous activators of TRPC3/6/7 channels, providing new insights into their regulatory mechanisms.

PubMed: 41125595
DOI: 10.1038/s41467-025-64435-6

Experimental method

ELECTRON MICROSCOPY (2.67 Å)