8SL8

Cryo-EM structure of the rat TRPM5 channel in trace calcium, trace-1

8SL8 の概要

• エントリーDOI: 10.2210/pdb8sl8/pdb
• EMDBエントリー: 40575 40600
• 分子名称: Transient receptor potential cation channel subfamily M member 5 (1 entity in total)
• 機能のキーワード: ion channel, transient receptor potential, trp, transient receptor potential melastatin 5, trpm5, 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: 529406.88

構造登録者

Karuppan, S.,Schrag, L.G.,Jara-Oseguera, A.,Zubcevic, L. (登録日: 2023-04-21, 公開日: 2024-07-03, 最終更新日: 2024-07-10)

主引用文献

Karuppan, S.,Schrag, L.G.,Pastrano, C.M.,Jara-Oseguera, A.,Zubcevic, L.
Structural dynamics at cytosolic interprotomer interfaces control gating of a mammalian TRPM5 channel.
Proc.Natl.Acad.Sci.USA, 121:e2403333121-e2403333121, 2024

PubMed Abstract: The transient receptor potential melastatin (TRPM) tetrameric cation channels are involved in a wide range of biological functions, from temperature sensing and taste transduction to regulation of cardiac function, inflammatory pain, and insulin secretion. The structurally conserved TRPM cytoplasmic domains make up >70 % of the total protein. To investigate the mechanism by which the TRPM cytoplasmic domains contribute to gating, we employed electrophysiology and cryo-EM to study TRPM5-a channel that primarily relies on activation via intracellular Ca. Here, we show that activation of mammalian TRPM5 channels is strongly altered by Ca-dependent desensitization. Structures of rat TRPM5 identify a series of conformational transitions triggered by Ca binding, whereby formation and dissolution of cytoplasmic interprotomer interfaces appear to control activation and desensitization of the channel. This study shows the importance of the cytoplasmic assembly in TRPM5 channel function and sets the stage for future investigations of other members of the TRPM family.

PubMed: 38923985
DOI: 10.1073/pnas.2403333121

実験手法

ELECTRON MICROSCOPY (4.2 Å)