Cryo-EM structure of TRPC5 at 2.8-Å resolution reveals unique and conserved structural elements essential for channel function. Sci Adv 2019 Jul;5(7):eaaw7935
Date
07/30/2019Pubmed ID
31355338Pubmed Central ID
PMC6656536DOI
10.1126/sciadv.aaw7935Scopus ID
2-s2.0-85069936406 (requires institutional sign-in at Scopus site) 86 CitationsAbstract
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.
Author List
Duan J, Li J, Chen GL, Ge Y, Liu J, Xie K, Peng X, Zhou W, Zhong J, Zhang Y, Xu J, Xue C, Liang B, Zhu L, Liu W, Zhang C, Tian XL, Wang J, Clapham DE, Zeng B, Li Z, Zhang JAuthors
Wei Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinLan Zhu PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsBinding Sites
Cations
Conserved Sequence
Cryoelectron Microscopy
Gadolinium
HEK293 Cells
Humans
Ion Channel Gating
Kinetics
Lanthanum
Lipids
Mice
Mutation
Structure-Activity Relationship
TRPC Cation Channels
