Cryo-EM structure of a proton-activated chloride channel TMEM206

Zengqin Deng, Yonghui Zhao, Jing Feng, Jingying Zhang, Haiyan Zhao, Michael J. Rau, James A.J. Fitzpatrick, Hongzhen Hu, Peng Yuan

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

TMEM206 has been recently identified as an evolutionarily conserved chloride channel that underlies ubiquitously expressed, proton-activated, outwardly rectifying anion currents. Here, we report the cryo–electron microscopy structure of pufferfish TMEM206, which forms a trimeric channel, with each subunit comprising two transmembrane segments and a large extracellular domain. An ample vestibule in the extracellular region is accessible laterally from the three side portals. The central pore contains multiple constrictions. A conserved lysine residue near the cytoplasmic end of the inner helix forms the presumed chloride ion selectivity filter. Unprecedentedly, the core structure and assembly closely resemble those of the epithelial sodium channel/degenerin family of sodium channels that are unrelated in amino acid sequence and conduct cations instead of anions. Together with electrophysiology, this work provides insights into ion conduction and gating for a new class of chloride channels that is architecturally distinct from previously characterized chloride channel families.

Original languageEnglish
Article numbereabe5983
JournalScience advances
Volume7
Issue number9
DOIs
StatePublished - 24 Feb 2021
Externally publishedYes

Fingerprint

Dive into the research topics of 'Cryo-EM structure of a proton-activated chloride channel TMEM206'. Together they form a unique fingerprint.

Cite this