1. Structural Biology and Molecular Biophysics
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Structure of the human lipid-gated cation channel TRPC3

  1. Chen Fan
  2. Wooyoung Choi
  3. Weinan Sun
  4. Juan Du  Is a corresponding author
  5. Wei Lu  Is a corresponding author
  1. Van Andel Institute, United States
  2. Vollum Institute, United States
Research Article
  • Cited 47
  • Views 3,735
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Cite this article as: eLife 2018;7:e36852 doi: 10.7554/eLife.36852

Abstract

The TRPC channels are crucially involved in store-operated calcium entry and calcium homeostasis, and they are implicated in human diseases such as neurodegenerative disease, cardiac hypertrophy, and spinocerebellar ataxia. We present a structure of the full-length human TRPC3, a lipid-gated TRPC member, in a lipid-occupied, closed state at 3.3 Angstrom. TRPC3 has four elbow-like membrane reentrant helices prior to the first transmembrane helix. The TRP helix is perpendicular to, and thus disengaged from, the pore-lining S6, suggesting a different gating mechanism from other TRP subfamily channels. The third transmembrane helix S3 is remarkably long, shaping a unique transmembrane domain, and constituting an extracellular domain that may serve as a sensor of external stimuli. We identified two lipid binding sites, one being sandwiched between the pre-S1 elbow and the S4-S5 linker, and the other being close to the ion-conducting pore, where the conserved LWF motif of the TRPC family is located.

Article and author information

Author details

  1. Chen Fan

    Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Wooyoung Choi

    Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Weinan Sun

    Vollum Institute, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Juan Du

    Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, United States
    For correspondence
    juan.du@vai.org
    Competing interests
    The authors declare that no competing interests exist.
  5. Wei Lu

    Center for Cancer and Cell Biology, Van Andel Institute, Grand Rapids, United States
    For correspondence
    wei.lu@vai.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3009-1025

Funding

Van Andel Research Institute

  • Wei Lu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Leon D. Islas, Universidad Nacional Autónoma de México, Mexico

Publication history

  1. Received: March 21, 2018
  2. Accepted: May 2, 2018
  3. Accepted Manuscript published: May 4, 2018 (version 1)
  4. Version of Record published: May 24, 2018 (version 2)
  5. Version of Record updated: October 3, 2019 (version 3)

Copyright

© 2018, Fan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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