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

Sigrid Noreng, Arpita Bharadwaj, Richard Posert, Craig Yoshioka, Isabelle Baconguis

Research output: Contribution to journalArticle

26 Scopus citations

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.

Original languageEnglish (US)
JournaleLife
Volume7
DOIs
StatePublished - Sep 25 2018

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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