8S90

Cryo-EM structure of octameric human CALHM1 (I109W) in complex with ruthenium red (C1)

8S90 の概要

• エントリーDOI: 10.2210/pdb8s90/pdb
• EMDBエントリー: 40233
• 分子名称: Calcium homeostasis modulator protein 1, ruthenium(6+) azanide pentaamino(oxido)ruthenium (1/4/2) (2 entities in total)
• 機能のキーワード: taste, assembly, calcium homeostasis modulator protein, membrane protein, channel, lipid binding, large-pore channel, ruthenium red
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 279299.84

構造登録者

Syrjanen, J.L.,Furukawa, H. (登録日: 2023-03-27, 公開日: 2023-07-26, 最終更新日: 2024-11-13)

主引用文献

Syrjanen, J.L.,Epstein, M.,Gomez, R.,Furukawa, H.
Structure of human CALHM1 reveals key locations for channel regulation and blockade by ruthenium red.
Nat Commun, 14:3821-3821, 2023

PubMed Abstract: Calcium homeostasis modulator 1 (CALHM1) is a voltage-dependent channel involved in neuromodulation and gustatory signaling. Despite recent progress in the structural biology of CALHM1, insights into functional regulation, pore architecture, and channel blockade remain limited. Here we present the cryo-EM structure of human CALHM1, revealing an octameric assembly pattern similar to the non-mammalian CALHM1s and the lipid-binding pocket conserved across species. We demonstrate by MD simulations that this pocket preferentially binds a phospholipid over cholesterol to stabilize its structure and regulate the channel activities. Finally, we show that residues in the amino-terminal helix form the channel pore that ruthenium red binds and blocks.

PubMed: 37380652
DOI: 10.1038/s41467-023-39388-3

実験手法

ELECTRON MICROSCOPY (4.73 Å)