Cryo-EM structure of TRPC5 at 2.8-Å resolution reveals unique and conserved structural elements essential for channel function

Jingjing Duan, Jian Li, Gui Lan Chen, Yan Ge, Jieyu Liu, Kechen Xie, Xiaogang Peng, Wei Zhou, Jianing Zhong, Yixing Zhang, Jie Xu, Changhu Xue, Bo Liang, Lan Zhu, Wei Liu, Cheng Zhang, Xiao Li Tian, Jianbin Wang, David E. Clapham, Bo ZengZongli Li, Jin Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

The transient receptor potential canonical subfamily member 5 (TRPC5), one of seven mammalian TRPC members, is a nonselective calcium-permeant cation channel. TRPC5 is of considerable interest as a drug target in the treatment of progressive kidney disease, depression, and anxiety. Here, we present the 2.8-Å resolution cryo–electron microscopy (cryo-EM) structure of the mouse TRPC5 (mTRPC5) homotetramer. Comparison of the TRPC5 structure to previously determined structures of other TRPC and TRP channels reveals differences in the extracellular pore domain and in the length of the S3 helix. The disulfide bond at the extracellular side of the pore and a preceding small loop are essential elements for its proper function. This high-resolution structure of mTRPC5, combined with electrophysiology and mutagenesis, provides insight into the lipid modulation and gating mechanisms of the TRPC family of ion channels.

Original languageEnglish (US)
Article numbereaaw7935
JournalScience Advances
Volume5
Issue number7
DOIs
StatePublished - Jul 24 2019
Externally publishedYes

ASJC Scopus subject areas

  • General

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