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

Xiaozhe Chen; Yaojie Wang; Yang Li; Xuhang Lu; Jianan Chen; Ming Li; Tianlei Wen; Ning Liu; Shenghai Chang; Xing Zhang; Xue Yang; Yuequan Shen

doi:10.1016/j.celrep.2022.110445

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

Cell Rep. 2022 Mar 1;38(9):110445. doi: 10.1016/j.celrep.2022.110445.

Authors

Xiaozhe Chen¹, Yaojie Wang¹, Yang Li¹, Xuhang Lu¹, Jianan Chen², Ming Li¹, Tianlei Wen¹, Ning Liu³, Shenghai Chang⁴, Xing Zhang⁴, Xue Yang⁵, Yuequan Shen⁶

Affiliations

¹ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300350, China; Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300350, China.
² State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300350, China; College of Pharmacy, Nankai University, Tianjin 300350, China.
³ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300350, China.
⁴ Department of Biophysics and Department of Pathology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310027, China; Center of Cryo Electron Microscopy, Zhejiang University School of Medicine, Hangzhou 310027, China.
⁵ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300350, China; Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300350, China. Electronic address: yangxue@nankai.edu.cn.
⁶ State Key Laboratory of Medicinal Chemical Biology and College of Life Sciences, Nankai University, Tianjin 300350, China; Frontiers Science Center for Cell Responses, Nankai University, Tianjin 300350, China; Synergetic Innovation Center of Chemical Science and Engineering, Tianjin 300071, China. Electronic address: yshen@nankai.edu.cn.

PMID: 35235791
DOI: 10.1016/j.celrep.2022.110445

Abstract

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.

Keywords: TACAN; channel; cholesterol; dimer; mechanism; mechanosensitive; pain; structure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Carrier Proteins*
Cryoelectron Microscopy
Humans
Ion Channels / chemistry*
Membranes
Pain*
Protein Domains
Protein Subunits

Substances

Carrier Proteins
Ion Channels
Protein Subunits