Cryo-EM structure of the human TACAN in a closed state

作者：Xiaozhe Chen, Yaojie Wang, Yang Li, Xuhang Lu, Jianan Chen, Ming Li, Tianlei Wen, Ning Liu, Shenghai Chang, Xing Zhang, Xue Yang, Yuequan Shen · 发表于：Cell Reports · 年份：2022 · DOI：10.1016/j.celrep.2022.110445 · 被引用次数：16 · 研究领域：Ion channel regulation and function、Cardiac electrophysiology and arrhythmias、Connexins and lens biology

TACAN is an ion channel-like protein that may be involved in sensing mechanical pain. Here, we present the cryo-electron microscopic structure of human TACAN (hTACAN). hTACAN forms a dimer in which each protomer consists of a transmembrane globular domain (TMD) containing six helices and an intracellular domain (ICD) containing two helices. Molecular dynamic simulations suggest that each protomer contains a putative ion conduction pore. A single-point mutation of the key residue Met207 greatly increases membrane pressure-activated currents. In addition, each hTACAN subunit binds one cholesterol molecule. Our data show the molecular assembly of hTACAN and suggest that wild-type hTACAN is in a closed state.