5zbg | pdb_00005zbg

Cryo-EM structure of human TRPC3 at 4.36A resolution

Loading... Status: waiting for Mol* initialization Structural highlights 5zbg is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: TRPC3, TRP3 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [TRPC3_HUMAN] The disease is caused by mutations affecting the gene represented in this entry. Function [TRPC3_HUMAN] Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C, and by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3. May also be activated by internal calcium store depletion. Publication Abstract from PubMed 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 A resolution. We also present the structure of human TRPC3 at 4.4 A 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. Structure of the receptor-activated human TRPC6 and TRPC3 ion channels.,Tang Q, Guo W, Zheng L, Wu JX, Liu M, Zhou X, Zhang X, Chen L Cell Res. 2018 Apr 26. pii: 10.1038/s41422-018-0038-2. doi:, 10.1038/s41422-018-0038-2. PMID:29700422 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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