6BWI

3.7 angstrom cryoEM structure of full length human TRPM4

6BWI の概要

• エントリーDOI: 10.2210/pdb6bwi/pdb
• EMDBエントリー: 7299
• 分子名称: Transient receptor potential cation channel subfamily M member 4, SODIUM ION, CHOLESTEROL HEMISUCCINATE, ... (4 entities in total)
• 機能のキーワード: cryoem, human full length trpm7, membrane 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: 430775.86

構造登録者

Zhang, J.,Li, Z.,Duan, J.,Li, J.,Clapham, D.E. (登録日: 2017-12-15, 公開日: 2018-12-19, 最終更新日: 2025-06-04)

主引用文献

Duan, J.,Li, Z.,Li, J.,Santa-Cruz, A.,Sanchez-Martinez, S.,Zhang, J.,Clapham, D.E.
Structure of full-length human TRPM4.
Proc.Natl.Acad.Sci.USA, 115:2377-2382, 2018

PubMed Abstract: Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini. Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites. We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.

PubMed: 29463718
DOI: 10.1073/pnas.1722038115

実験手法

ELECTRON MICROSCOPY (3.7 Å)