8V6K

Apo-state cryo-EM structure of human TRPV3 in cNW30 nanodiscs

8V6K の概要

• エントリーDOI: 10.2210/pdb8v6k/pdb
• EMDBエントリー: 42994
• 分子名称: Transient receptor potential cation channel subfamily V member 3, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: transient receptor potential v family member 3, trp, channel, trpv3, trp channels, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 395134.46

構造登録者

Nadezhdin, K.D.,Neuberger, A.,Sobolevsky, A.I. (登録日: 2023-12-01, 公開日: 2024-04-17, 最終更新日: 2024-11-06)

主引用文献

Nadezhdin, K.D.,Neuberger, A.,Khosrof, L.S.,Talyzina, I.A.,Khau, J.,Yelshanskaya, M.V.,Sobolevsky, A.I.
TRPV3 activation by different agonists accompanied by lipid dissociation from the vanilloid site.
Sci Adv, 10:eadn2453-eadn2453, 2024

PubMed Abstract: 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.

PubMed: 38691614
DOI: 10.1126/sciadv.adn2453

実験手法

ELECTRON MICROSCOPY (2.46 Å)