9MT8

Cryo-EM structure of the human TRPM4 channel in a calcium bound putative desensitized state

9MT8 の概要

• エントリーDOI: 10.2210/pdb9mt8/pdb
• 関連するPDBエントリー: 9MRT
• EMDBエントリー: 48563 48603
• 分子名称: Transient receptor potential cation channel subfamily M member 4, CALCIUM ION (2 entities in total)
• 機能のキーワード: trpm4, ion channel, transport 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: 537986.25

構造登録者

Teixeira-Duarte, C.M.,Jiang, Y. (登録日: 2025-01-10, 公開日: 2025-10-29, 最終更新日: 2025-11-12)

主引用文献

Teixeira-Duarte, C.M.,Zeng, W.,Jiang, Y.
Structural landscape of activation, desensitization and inhibition in the human TRPM4 channel.
Nat.Struct.Mol.Biol., 2025

PubMed Abstract: TRPM4 is a member of the transient receptor potential melastatin channel subfamily and functions as a Ca-activated monovalent-selective cation channel. It is widely expressed in various cells and tissues, where its activation depolarizes the plasma membrane potential and modulates various Ca-dependent biological processes. TRPM4 activity is potentiated by membrane phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P) and inhibited by cytosolic free adenosine triphosphate (ATP), allowing the channel to transition between different functional states in response to dynamic changes in cellular Ca, ATP and PtdIns(4,5)P levels during signaling events. Here we present single-particle cryo-electron microscopy structures of human TRPM4 in four distinct states: apo closed, Ca-bound putative desensitized, Ca-PtdIns(4,5)P-bound open and ATP-bound inhibited. Combined with mutagenesis and electrophysiological analyses, these structures reveal the molecular mechanisms underlying TRPM4 activation, desensitization and inhibition. Given the central roles of Ca, PtdIns(4,5)P and ATP in cellular signaling, this work provides a structural foundation to decipher the physiological functions of TRPM4 across diverse biological systems.

PubMed: 41174278
DOI: 10.1038/s41594-025-01705-3

実験手法

ELECTRON MICROSCOPY (3.19 Å)