Structure of the human epithelial sodium channel by cryo-electron microscopy
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.
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ΔENaC model coordinatesAvailable at PDB, freely with attribution, provided the user agrees to abide by the conditions described in the PDB Advisory Notice.
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ΔENaC map, FSCAvailable 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
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
- Sriram Subramaniam, National Cancer Institute, United States
Version history
- Received: June 19, 2018
- Accepted: September 18, 2018
- Accepted Manuscript published: September 25, 2018 (version 1)
- Version of Record published: October 22, 2018 (version 2)
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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Further reading
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