9KHI

Cryo-EM structure of heteromeric TRPC channel

Summary for 9KHI

• Entry DOI: 10.2210/pdb9khi/pdb
• EMDB information: 62343
• Descriptor: Short transient receptor potential channel 1, Short transient receptor potential channel 5, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: trp, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 4
• Total formula weight: 365105.32

Authors

Kim, S.-H.,Lee, H.H. (deposition date: 2024-11-10, release date: 2025-11-12, Last modification date: 2026-01-21)

Primary citation

Kim, S.H.,Park, H.,Kim, J.,Kang, H.,Won, J.,Lee, B.C.,So, I.,Lee, H.H.
Molecular architecture of the human TRPC1/C5 heteromeric channel.
Nat Commun, 17:317-317, 2025

PubMed Abstract: Transient receptor potential (TRP) ion channels form heteromers through combinatorial associations of distinct subunits, contributing to the diversity of TRP channel functions. Among them, TRPC5, which forms a heteromer with TRPC1, represents an attractive pharmaceutical target for treating anxiety and depression. Here, we present the cryo-electron microscopy structure of the human TRPC1/C5 heteromer, composed of one TRPC1 subunit and three TRPC5 subunits. The incorporation of TRPC1 into the heteromer disrupts the C symmetry of the TRPC5 homotetramer, resulting in a distinct ion conduction pathway characterized by an asymmetrically constricted selectivity filter and an asymmetric lower gate. The TRPC1/C5 heteromer displays recognizable structural features compared to the TRPC1/C4 heteromer, including a noncanonically tilted coiled-coil domain and a distinct intersubunit interactions. Furthermore, we elucidate the structures of human TRPC5 bound to the TRPC1/4/5-specific agonist, (-)-Englerin A. Our findings establish a foundation for exploring the diversity of heteromeric TRP channels and pave the way for targeting TRPC1/C5 as a therapeutic strategy.

PubMed: 41372144
DOI: 10.1038/s41467-025-67024-9

Experimental method

ELECTRON MICROSCOPY (2.7 Å)