7JNC

cryo-EM structure of human proton-activated chloride channel PAC at pH 4

7JNC の概要

• エントリーDOI: 10.2210/pdb7jnc/pdb
• 関連するPDBエントリー: 7JNA
• EMDBエントリー: 22403 22404
• 分子名称: Proton-activated chloride channel, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: pac, pacc1, paorac, asor, tmem206, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 123540.22

構造登録者

Lu, W.,Ruan, R.,Du, J. (登録日: 2020-08-04, 公開日: 2020-11-11, 最終更新日: 2025-05-28)

主引用文献

Ruan, Z.,Osei-Owusu, J.,Du, J.,Qiu, Z.,Lu, W.
Structures and pH-sensing mechanism of the proton-activated chloride channel.
Nature, 588:350-354, 2020

PubMed Abstract: The proton-activated chloride channel (PAC) is active across a wide range of mammalian cells and is involved in acid-induced cell death and tissue injury. PAC has recently been shown to represent a novel and evolutionarily conserved protein family. Here we present two cryo-electron microscopy structures of human PAC in a high-pH resting closed state and a low-pH proton-bound non-conducting state. PAC is a trimer in which each subunit consists of a transmembrane domain (TMD), which is formed of two helices (TM1 and TM2), and an extracellular domain (ECD). Upon a decrease of pH from 8 to 4, we observed marked conformational changes in the ECD-TMD interface and the TMD. The rearrangement of the ECD-TMD interface is characterized by the movement of the histidine 98 residue, which is, after acidification, decoupled from the resting position and inserted into an acidic pocket that is about 5 Å away. Within the TMD, TM1 undergoes a rotational movement, switching its interaction partner from its cognate TM2 to the adjacent TM2. The anion selectivity of PAC is determined by the positively charged lysine 319 residue on TM2, and replacing lysine 319 with a glutamate residue converts PAC to a cation-selective channel. Our data provide a glimpse of the molecular assembly of PAC, and a basis for understanding the mechanism of proton-dependent activation.

PubMed: 33149300
DOI: 10.1038/s41586-020-2875-7

実験手法

ELECTRON MICROSCOPY (3.73 Å)