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Elife. 2018 Sep 25;7. pii: e39340. doi: 10.7554/eLife.39340.

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

Author information

1
Department of Biochemistry & Molecular Biology, Oregon Health and Science University, Portland, United States.
2
Vollum Institute, Oregon Health and Science University, Portland, United States.
3
Department of Biomedical Engineering, Oregon Health and Science University, Portland, 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.

KEYWORDS:

Cryo-EM; Ion Channel; electrophysiology; heterotrimer; human; molecular biophysics; structural biology; structure

PMID:
30251954
PMCID:
PMC6197857
DOI:
10.7554/eLife.39340
[Indexed for MEDLINE]
Free PMC Article

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