5WKV

Structure of an acid sensing ion channel in a resting state with calcium

5WKV の概要

• エントリーDOI: 10.2210/pdb5wkv/pdb
• 関連するPDBエントリー: 5WKU 6AVE
• EMDBエントリー: 7009
• 分子名称: Acid-sensing ion channel 1, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: ion channel, asic, asic1a, sodium channel, transport protein, membrane protein
• 由来する生物種: Gallus gallus (Chicken)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 152768.49

構造登録者

Yoder, N.,Gouaux, E. (登録日: 2017-07-25, 公開日: 2018-03-14, 最終更新日: 2024-10-30)

主引用文献

Yoder, N.,Yoshioka, C.,Gouaux, E.
Gating mechanisms of acid-sensing ion channels.
Nature, 555:397-401, 2018

PubMed Abstract: Acid-sensing ion channels (ASICs) are trimeric, proton-gated and sodium-selective members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout vertebrate central and peripheral nervous systems. Gating of ASICs occurs on a millisecond time scale and the mechanism involves three conformational states: high pH resting, low pH open and low pH desensitized. Existing X-ray structures of ASIC1a describe the conformations of the open and desensitized states, but the structure of the high pH resting state and detailed mechanisms of the activation and desensitization of the channel have remained elusive. Here we present structures of the high pH resting state of homotrimeric chicken (Gallus gallus) ASIC1a, determined by X-ray crystallography and single particle cryo-electron microscopy, and present a comprehensive molecular mechanism for proton-dependent gating in ASICs. In the resting state, the position of the thumb domain is further from the three-fold molecular axis, thereby expanding the 'acidic pocket' in comparison to the open and desensitized states. Activation therefore involves 'closure' of the thumb into the acidic pocket, expansion of the lower palm domain and an iris-like opening of the channel gate. Furthermore, we demonstrate how the β11-β12 linkers that demarcate the upper and lower palm domains serve as a molecular 'clutch', and undergo a simple rearrangement to permit rapid desensitization.

PubMed: 29513651
DOI: 10.1038/nature25782

実験手法

X-RAY DIFFRACTION (3.2 Å)