2. Academic Validation
  3. Structure of the mouse TRPC4 ion channel

Structure of the mouse TRPC4 ion channel

  • Nat Commun. 2018 Aug 6;9(1):3102. doi: 10.1038/s41467-018-05247-9.
Jingjing Duan 1 2,  Jian Li 1 3,  Bo Zeng 4,  Gui-Lan Chen 4,  Xiaogang Peng 5,  Yixing Zhang 1,  Jianbin Wang 1,  David E Clapham 2,  Zongli Li 6,  Jin Zhang 7
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences, Nanchang University, 330031, Nanchang, Jiangxi, China.
  • 2 Howard Hughes Medical Institute, Janelia Research Campus, Ashburn, VA, 20147, USA.
  • 3 Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY, 40536, USA.
  • 4 Key Laboratory of Medical Electrophysiology, Ministry of Education, and Institute of Cardiovascular Research, Southwest Medical University, 646000, Luzhou, Sichuan, China.
  • 5 The Key Laboratory of Molecular Medicine, The Second Affiliated Hospital of Nanchang University, 330006, Nanchang, China.
  • 6 Department of Biological Chemistry and Molecular Pharmacology, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, 02115, USA. [email protected].
  • 7 School of Basic Medical Sciences, Nanchang University, 330031, Nanchang, Jiangxi, China. [email protected].
PMID: 30082700 DOI: 10.1038/s41467-018-05247-9
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.

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