8v6m

Inactivated-state cryo-EM structure of human TRPV3 in presence of tetrahydrocannabivarin (THCV) in cNW30 nanodiscs

spinqualitylabelsall models 8v6m, resolution 3.63Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8v6m is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.63Å Ligands: I8E, NA, POV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed TRPV3 represents both temperature- and ligand-activated transient receptor potential (TRP) channel. Physiologically relevant opening of TRPV3 channels by heat has been captured structurally, while opening by agonists has only been observed in structures of mutant channels. Here, we present cryo-EM structures that illuminate opening and inactivation of wild-type human TRPV3 in response to binding of two types of agonists: either the natural cannabinoid tetrahydrocannabivarin (THCV) or synthetic agonist 2-aminoethoxydiphenylborane (2-APB). We found that THCV binds to the vanilloid site, while 2-APB binds to the S1-S4 base and ARD-TMD linker sites. Despite binding to distally located sites, both agonists induce similar pore opening and cause dissociation of a lipid that occupies the vanilloid site in their absence. Our results uncover different but converging allosteric pathways through which small-molecule agonists activate TRPV3 and provide a framework for drug design and understanding the role of lipids in ion channel function. TRPV3 activation by different agonists accompanied by lipid dissociation from the vanilloid site.,Nadezhdin KD, Neuberger A, Khosrof LS, Talyzina IA, Khau J, Yelshanskaya MV, Sobolevsky AI Sci Adv. 2024 May 3;10(18):eadn2453. doi: 10.1126/sciadv.adn2453. Epub 2024 May , 1. PMID:38691614 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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