9LEV

Cryo-EM structure of human ZAC in nanodisc in apo state

9LEV の概要

• エントリーDOI: 10.2210/pdb9lev/pdb
• EMDBエントリー: 63035
• 分子名称: Ligand-gated cation channel ZACN,Genome polyprotein, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: cys-loop receptor, homopentamer, cation channel, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 399209.01

構造登録者

Qu, Q.,Zhou, Z. (登録日: 2025-01-07, 公開日: 2026-04-22)

主引用文献

Zhou, Z.,Long, Y.,Chao, Y.,Yang, C.,Tang, Y.Q.,Shu, Y.,Zhu, H.,Jensen, A.A.,Qu, Q.
Structural basis of human zinc-activated channel (ZAC) signaling and modulation.
Cell Discov, 12:-, 2026

PubMed Abstract: Zinc (Zn) plays essential roles in a plethora of physiological processes, including key functions as a neuromodulator. The zinc-activated channel (ZAC) belongs to the Cys-loop receptor (CLR) superfamily of pentameric ligand-gated ion channels, which also comprises receptors for the important neurotransmitters acetylcholine, serotonin, GABA and glycine. In contrast to these classical CLRs, which have been extensively explored over decades, ZAC remains poorly characterized despite its potential significance in mammals. Here, we present several cryo-EM structures of human ZAC, including the ligand-free resting state, the Zn-bound state, and several antagonist-bound states. In the Zn-bound structure, Zn ions bind to the subunit interfaces of the extracellular domain, corresponding to the canonical agonist-binding sites in the classical CLRs, and are primarily coordinated through cation‒π interactions with two aromatic residues. While the antagonist TTFB inhibits ZAC by insertion between the transmembrane M2 helices of adjacent subunits, d-tubocurarine acts in a dual manner by blocking the channel and interfering with agonist binding. Combined with mutagenesis and electrophysiological analysis, these evaluations highlight the distinctive structural and functional features of this atypical CLR.

PubMed: 41912481
DOI: 10.1038/s41421-026-00878-5

実験手法

ELECTRON MICROSCOPY (3.35 Å)