Structure of the human epithelial sodium channel by cryo-electron microscopy
- Oregon Health and Science University, United States
- 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.
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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
Isabelle Baconguis
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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Structure of the human epithelial sodium channel by cryo-electron microscopy
eLife 7:e39340.
https://doi.org/10.7554/eLife.39340
Further reading
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eLife has published papers on topics related to the molecular structure and functional mechanisms of a diverse array of ion channel proteins.
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