5YX9

Cryo-EM structure of human TRPC6 at 3.8A resolution

Summary for 5YX9

• Entry DOI: 10.2210/pdb5yx9/pdb
• EMDB information: 6856
• Descriptor: Short transient receptor potential channel 6 (1 entity in total)
• Functional Keywords: trpc6 channel, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 425812.97

Authors

Chen, L.,Tang, Q.,Guo, W. (deposition date: 2017-12-02, release date: 2018-05-23, Last modification date: 2024-03-27)

Primary citation

Tang, Q.,Guo, W.,Zheng, L.,Wu, J.X.,Liu, M.,Zhou, X.,Zhang, X.,Chen, L.
Structure of the receptor-activated human TRPC6 and TRPC3 ion channels.
Cell Res., 28:746-755, 2018

PubMed Abstract: TRPC6 and TRPC3 are receptor-activated nonselective cation channels that belong to the family of canonical transient receptor potential (TRPC) channels. They are activated by diacylglycerol, a lipid second messenger. TRPC6 and TRPC3 are involved in many physiological processes and implicated in human genetic diseases. Here we present the structure of human TRPC6 homotetramer in complex with a newly identified high-affinity inhibitor BTDM solved by single-particle cryo-electron microscopy to 3.8 Å resolution. We also present the structure of human TRPC3 at 4.4 Å resolution. These structures show two-layer architectures in which the bell-shaped cytosolic layer holds the transmembrane layer. Extensive inter-subunit interactions of cytosolic domains, including the N-terminal ankyrin repeats and the C-terminal coiled-coil, contribute to the tetramer assembly. The high-affinity inhibitor BTDM wedges between the S5-S6 pore domain and voltage sensor-like domain to inhibit channel opening. Our structures uncover the molecular architecture of TRPC channels and provide a structural basis for understanding the mechanism of these channels.

PubMed: 29700422
DOI: 10.1038/s41422-018-0038-2

Experimental method

ELECTRON MICROSCOPY (3.8 Å)