Abstract
Members of the transient receptor potential (TRP) ion channels conduct cations into cells. They mediate functions ranging from neuronally mediated hot and cold sensation to intracellular organellar and primary ciliary signaling. Here we report a cryo-electron microscopy (cryo-EM) structure of TRPC4 in its unliganded (apo) state to an overall resolution of 3.3 Å. The structure reveals a unique architecture with a long pore loop stabilized by a disulfide bond. Beyond the shared tetrameric six-transmembrane fold, the TRPC4 structure deviates from other TRP channels with a unique cytosolic domain. This unique cytosolic N-terminal domain forms extensive aromatic contacts with the TRP and the C-terminal domains. The comparison of our structure with other known TRP structures provides molecular insights into TRPC4 ion selectivity and extends our knowledge of the diversity and evolution of the TRP channels.
Document Type
Article
Publication Date
8-6-2018
Digital Object Identifier (DOI)
https://doi.org/10.1038/s41467-018-05247-9
Funding Information
J.Z. was supported by the Thousand Young Talents Program of China and National Natural Science Foundation of China (Grant No. 31770795). J.L. was supported by the National Natural Science Foundation of China (Grant No. 81402850). Functional studies in this project were supported by the National Natural Science Foundation of China (31300949 to B.Z. and 31300965 to G.-L.C.)
Related Content
Data supporting the findings of this manuscript are available from the corresponding authors upon reasonable request. Data deposition: Cryo-EM electron density map of the mouse TRPC4 has been deposited in the Electron Microscopy Data Bank, [EMD:6901] https://www.ebi.ac.uk/pdbe/emdb/, and the fitted coordinate has been deposited in the Protein Data Bank, [PDB:5Z96] www.pdb.org.
Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467-018-05247-9.
Repository Citation
Duan, Jingjing; Li, Jian; Zeng, Bo; Chen, Gui-Lan; Peng, Xiaogang; Zhang, Yixing; Wang, Jianbin; Clapham, David E.; Li, Zongli; and Zhang, Jin, "Structure of the Mouse TRPC4 Ion Channel" (2018). Molecular and Cellular Biochemistry Faculty Publications. 152.
https://uknowledge.uky.edu/biochem_facpub/152
Supplementary Information
41467_2018_5247_MOESM2_ESM.pdf (221 kB)
Peer Review File
Included in
Biochemistry, Biophysics, and Structural Biology Commons, Cell and Developmental Biology Commons
Notes/Citation Information
Published in Nature Communications, v. 9, article no. 3102, p. 1-10.
© The Author(s) 2018
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