Structure of the human epithelial sodium channel by cryo-electron microscopy

  1. Sigrid Noreng
  2. Arpita Bharadwaj
  3. Richard Posert
  4. Craig Yoshioka
  5. Isabelle Baconguis  Is a corresponding author
  1. Oregon Health and Science University, United States
  2. Vollum Institute, United States

Abstract

The epithelial sodium channel (ENaC), a member of the ENaC/DEG superfamily, regulates Na+ and water homeostasis. ENaCs assemble as heterotrimeric channels that harbor protease-sensitive domains critical for gating the channel. Here we present the structure of human ENaC in the uncleaved state determined by single-particle cryo-electron microscopy. The ion channel is composed of a large extracellular domain and a narrow transmembrane domain. The structure reveals that ENaC assembles with a 1:1:1 stoichiometry of α:β:γ subunits arranged in a counter-clockwise manner. The shape of each subunit is reminiscent of a hand with key gating domains of a 'finger' and a 'thumb'. Wedged between these domains is the elusive protease-sensitive inhibitory domain poised to regulate conformational changes of the 'finger' and 'thumb'; thus, the structure provides the first view of the architecture of inhibition of ENaC.

Data availability

The three-dimensional cryo-EM density map and the coordinate for the structure of ΔENAC have been deposited in the EM Database and Protein Data Bank under the accession codes EMD-7130 and 6BQN, respectively.

The following data sets were generated
    1. Noreng S
    2. Bharadwaj A
    3. Posert R
    4. Yoshioka C
    5. Baconguis I
    (2018) ΔENaC model coordinates
    Available at PDB, freely with attribution, provided the user agrees to abide by the conditions described in the PDB Advisory Notice.
    1. Noreng S
    2. Bharadwaj A
    3. Posert R
    4. Yoshioka C
    5. Baconguis I
    (2018) ΔENaC map, FSC
    Available at PDB, freely with attribution, provided the user agrees to abide by the conditions described in the PDB Advisory Notice.

Article and author information

Author details

  1. Sigrid Noreng

    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Arpita Bharadwaj

    Vollum Institute, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Richard Posert

    Department of Biochemistry and Molecular Biology, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9010-2104
  4. Craig Yoshioka

    Department of Biomedical Engineering, Oregon Health and Science University, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0251-7316
  5. Isabelle Baconguis

    Vollum Institute, Portland, United States
    For correspondence
    bacongui@ohsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5440-2289

Funding

National Institutes of Health (DP5OD017871)

  • Isabelle Baconguis

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

Copyright

© 2018, Noreng 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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  1. Sigrid Noreng
  2. Arpita Bharadwaj
  3. Richard Posert
  4. Craig Yoshioka
  5. Isabelle Baconguis
(2018)
Structure of the human epithelial sodium channel by cryo-electron microscopy
eLife 7:e39340.
https://doi.org/10.7554/eLife.39340

Share this article

https://doi.org/10.7554/eLife.39340

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