5WP6

Cryo-EM structure of a human TRPM4 channel in complex with calcium and decavanadate

5WP6 の概要

• エントリーDOI: 10.2210/pdb5wp6/pdb
• EMDBエントリー: 8871 8872 8875 8876 8877 8878 8879
• 分子名称: Transient receptor potential cation channel subfamily M member 4, DECAVANADATE (2 entities in total)
• 機能のキーワード: ion channel, membrane protein
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 1: Cell membrane; Multi-pass membrane protein. Isoform 2: Endoplasmic reticulum: Q8TD43
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 545485.12

構造登録者

Winkler, P.A.,Huang, Y.,Sun, W.,Du, J.,Lu, W. (登録日: 2017-08-03, 公開日: 2017-12-13, 最終更新日: 2025-05-28)

主引用文献

Winkler, P.A.,Huang, Y.,Sun, W.,Du, J.,Lu, W.
Electron cryo-microscopy structure of a human TRPM4 channel.
Nature, 552:200-204, 2017

PubMed Abstract: Ca-activated, non-selective (CAN) ion channels sense increases of the intracellular Ca concentration, producing a flux of Na and/or K ions that depolarizes the cell, thus modulating cellular Ca entry. CAN channels are involved in cellular responses such as neuronal bursting activity and cardiac rhythm. Here we report the electron cryo-microscopy structure of the most widespread CAN channel, human TRPM4, bound to the agonist Ca and the modulator decavanadate. Four cytosolic C-terminal domains form an umbrella-like structure with a coiled-coil domain for the 'pole' and four helical 'ribs' spanning the N-terminal TRPM homology regions (MHRs), thus holding four subunits in a crown-like architecture. We observed two decavanadate-binding sites, one in the C-terminal domain and another in the intersubunit MHR interface. A glutamine in the selectivity filter may be an important determinant of monovalent selectivity. Our structure provides new insights into the function and pharmacology of both the CAN and the TRPM families.

PubMed: 29211723
DOI: 10.1038/nature24674

実験手法

ELECTRON MICROSCOPY (3.8 Å)