9B3X

Rat TRPV2 E724A/D725A bound to 2-APB

9B3X の概要

• エントリーDOI: 10.2210/pdb9b3x/pdb
• EMDBエントリー: 44159
• 分子名称: Transient receptor potential cation channel subfamily V member 2, 1,2-DIDECANOYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE, 2-aminoethyl diphenylborinate (3 entities in total)
• 機能のキーワード: trpv2, trp channel, ion channel, 2-apb, membrane protein
• 由来する生物種: Rattus norvegicus (Norway rat)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 349778.28

構造登録者

Pumroy, R.A.,Rocereta, J.A.,Moiseenkova-Bell, V.Y. (登録日: 2024-03-20, 公開日: 2025-02-26, 最終更新日: 2025-07-02)

主引用文献

Rocereta, J.A.,Sturhahn, T.,Pumroy, R.A.,Fricke, T.C.,Herzog, C.,Leffler, A.,Moiseenkova-Bell, V.
Structural insights into TRPV2 modulation by probenecid.
Nat.Struct.Mol.Biol., 32:1019-1029, 2025

PubMed Abstract: The transient receptor potential vanilloid 2 (TRPV2) cation channel is a key player in cardiovascular physiology and pathophysiology. Probenecid (PBC), an FDA-approved uricosuric agent thought to activate TRPV2, has shown promise in enhancing cardiovascular function in both preclinical and clinical studies. Here our electrophysiological data reveal that PBC significantly potentiates rat TRPV2 to known stimuli, and cryo electron microscopy structures show that PBC directly interacts with rat TRPV2 in a previously unidentified intracellular binding pocket. PBC binding at a conserved TRPV2-specific histidine prevents the channel from taking on the inactivated carboxyl-terminal conformation. This effect extends to TRPV1 and TRPV3 channels when glutamine is substituted with histidine at the corresponding position, increasing their sensitivity to PBC. While PBC alone does not induce TRPV2 opening, its combination with 2-aminoethoxydiphenyl borate enables the channel to adopt an intermediate, potentiated state. Our results offer insights into potential therapeutic advancements for TRPV2 through this pocket.

PubMed: 39972168
DOI: 10.1038/s41594-025-01494-9

実験手法

ELECTRON MICROSCOPY (3.2 Å)