8U3C

TRPV1 in nanodisc bound with PI-Br4 bound in Conformation 2 (monomer)

8U3C の概要

• エントリーDOI: 10.2210/pdb8u3c/pdb
• EMDBエントリー: 41857
• 分子名称: Transient receptor potential cation channel subfamily V member 1, (2S)-2-[(9,10-dibromooctadecanoyl)oxy]-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,3,4,5,6-pentahydroxycyclohexyl]oxy}phosphoryl]oxy}propyl (9R,10S)-9,10-dibromooctadecanoate, 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE, ... (6 entities in total)
• 機能のキーワード: trpv1 in nanodisc bound with pi-br4 bound in conformation 2 (monomer), membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 188006.18

構造登録者

Arnold, W.R.,Julius, D.,Cheng, Y. (登録日: 2023-09-07, 公開日: 2024-05-08, 最終更新日: 2024-10-02)

主引用文献

Arnold, W.R.,Mancino, A.,Moss 3rd, F.R.,Frost, A.,Julius, D.,Cheng, Y.
Structural basis of TRPV1 modulation by endogenous bioactive lipids.
Nat.Struct.Mol.Biol., 31:1377-1385, 2024

PubMed Abstract: TRP ion channels are modulated by phosphoinositide lipids, but the underlying structural mechanisms remain unclear. The capsaicin- and heat-activated receptor, TRPV1, has served as a model for deciphering lipid modulation, which is relevant to understanding how pro-algesic agents enhance channel activity in the setting of inflammatory pain. Identification of a pocket within the TRPV1 transmembrane core has provided initial clues as to how phosphoinositide lipids bind to and regulate the channel. Here we show that this regulatory pocket in rat TRPV1 can accommodate diverse lipid species, including the inflammatory lipid lysophosphatidic acid, whose actions are determined by their specific modes of binding. Furthermore, we show that an empty-pocket channel lacking an endogenous phosphoinositide lipid assumes an agonist-like state, even at low temperature, substantiating the concept that phosphoinositide lipids serve as negative TRPV1 modulators whose ejection from the binding pocket is a critical step toward activation by thermal or chemical stimuli.

PubMed: 38698206
DOI: 10.1038/s41594-024-01299-2

実験手法

ELECTRON MICROSCOPY (2.3 Å)