9P3R

Zebrafish TRPM5 D797A mutant with 5mM calcium and 0.5mM CBTA

9P3R の概要

• エントリーDOI: 10.2210/pdb9p3r/pdb
• EMDBエントリー: 71252
• 分子名称: Transient receptor potential cation channel subfamily M member 5, 2-acetamido-2-deoxy-beta-D-glucopyranose, CALCIUM ION (3 entities in total)
• 機能のキーワード: trpm5 channel, ion channel, cation channel, sodium channel, transport protein
• 由来する生物種: Danio rerio (zebrafish)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 529458.27

構造登録者

Ruan, Z.,Du, J.,Lu, W. (登録日: 2025-06-14, 公開日: 2026-01-07, 最終更新日: 2026-03-11)

主引用文献

Ruan, Z.,Lee, J.,Li, Y.,Orozco, I.J.,Du, J.,Lu, W.
A single allosteric site merges activation, modulation and inhibition in TRPM5.
Nat.Chem.Biol., 22:402-410, 2026

PubMed Abstract: TRPM5 is a Ca-activated monovalent cation channel essential for taste perception, insulin secretion and gastrointestinal chemosensation. Canonical TRPM5 activation requires Ca binding at two distinct sites: an agonist site within the lower vestibule of the S1-S4 pocket in the transmembrane domain (Ca) and a modulatory site in the intracellular domain (Ca) that tunes voltage dependence and agonist sensitivity. Here we characterize CBTA as a noncalcium agonist that binds to the upper vestibule of the S1-S4 pocket, directly above Ca. CBTA alone mimics the dual role of Ca and Ca, merging agonist activation with voltage modulation. CBTA also renders TRPM5 supersensitive to Ca, synergistically hyperactivating the channel even at near-resting Ca levels. We further demonstrate that the inhibitor triphenylphosphine oxide binds the same site but stabilizes a nonconductive state. These opposing effects reveal the upper S1-S4 pocket as a multifunctional regulatory hub integrating activation, inhibition and modulation in TRPM5.

PubMed: 41491833
DOI: 10.1038/s41589-025-02097-7

実験手法

ELECTRON MICROSCOPY (3.5 Å)