6VAI

Cryo-EM structure of a dimer of undecameric human CALHM2

6VAI の概要

• エントリーDOI: 10.2210/pdb6vai/pdb
• EMDBエントリー: 21140 21141 21142 21143
• 分子名称: Calcium homeostasis modulator protein 2 (1 entity in total)
• 機能のキーワード: taste, assembly, calcium, gap junction, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 22
• 化学式量合計: 869329.05

構造登録者

Syrjanen, J.L.,Chou, T.H.,Furukawa, H. (登録日: 2019-12-17, 公開日: 2020-01-29, 最終更新日: 2024-11-06)

主引用文献

Syrjanen, J.L.,Michalski, K.,Chou, T.H.,Grant, T.,Rao, S.,Simorowski, N.,Tucker, S.J.,Grigorieff, N.,Furukawa, H.
Structure and assembly of calcium homeostasis modulator proteins.
Nat.Struct.Mol.Biol., 27:150-159, 2020

PubMed Abstract: The biological membranes of many cell types contain large-pore channels through which a wide variety of ions and metabolites permeate. Examples include connexin, innexin and pannexin, which form gap junctions and/or bona fide cell surface channels. The most recently identified large-pore channels are the calcium homeostasis modulators (CALHMs), through which ions and ATP permeate in a voltage-dependent manner to control neuronal excitability, taste signaling and pathologies of depression and Alzheimer's disease. Despite such critical biological roles, the structures and patterns of their oligomeric assembly remain unclear. Here, we reveal the structures of two CALHMs, chicken CALHM1 and human CALHM2, by single-particle cryo-electron microscopy (cryo-EM), which show novel assembly of the four transmembrane helices into channels of octamers and undecamers, respectively. Furthermore, molecular dynamics simulations suggest that lipids can favorably assemble into a bilayer within the larger CALHM2 pore, but not within CALHM1, demonstrating the potential correlation between pore size, lipid accommodation and channel activity.

PubMed: 31988524
DOI: 10.1038/s41594-019-0369-9

実験手法

ELECTRON MICROSCOPY (3.68 Å)