RT Journal Article
SR Electronic
T1 Cryo-EM structure of the receptor-activated TRPC5 ion channel at 2.9 angstrom resolution
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 467969
DO 10.1101/467969
A1 Jingjing Duan
A1 Jian Li
A1 Gui-Lan Chen
A1 Bo Zeng
A1 Kechen Xie
A1 Xiaogang Peng
A1 Wei Zhou
A1 Jianing Zhong
A1 Yixing Zhang
A1 Jie Xu
A1 Changhu Xue
A1 Lan Zhu
A1 Wei Liu
A1 Xiao-Li Tian
A1 Jianbin Wang
A1 David E. Clapham
A1 Zongli Li
A1 Jin Zhang
YR 2018
UL http://biorxiv.org/content/early/2018/11/11/467969.abstract
AB The transient receptor potential canonical subfamily member 5 (TRPC5) is a non-selective calcium-permeant cation channel. As a depolarizing channel, its function is studied in the central nervous system and kidney. TRPC5 forms heteromultimers with TRPC1, but also forms homomultimers. It can be activated by reducing agents through reduction of the extracellular disulfide bond. Here we present the 2.9 Å resolution electron cryo-microscopy (cryo-EM) structure of TRPC5. The structure of TRPC5 in its apo state is partially open, which may be related to the weak activation of TRPC5 in response to extracellular pH. We also report the conserved negatively charged residues of the cation binding site located in the hydrophilic pocket between S2 and S3. 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. Together, these results shed light on the structural features that contribute to the specific activation mechanism of the receptor-activated TRPC5.