1. Structural Biology and Molecular Biophysics
Download icon

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
Research Article
  • Cited 0
  • Views 1,743
  • Annotations
Cite this article as: eLife 2018;7:e39340 doi: 10.7554/eLife.39340

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.

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.

Reviewing Editor

  1. Sriram Subramaniam, National Cancer Institute, United States

Publication history

  1. Received: June 19, 2018
  2. Accepted: September 18, 2018
  3. Accepted Manuscript published: September 25, 2018 (version 1)

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.

Metrics

  • 1,743
    Page views
  • 540
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics
    Nicholas Chim et al.
    Short Report
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics
    Wen-Fan Shen et al.
    Research Article