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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 ?:?:? 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.

SUBMITTER: Noreng S

PROVIDER: S-EPMC6197857 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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

Noreng Sigrid S Bharadwaj Arpita A Posert Richard R Yoshioka Craig C Baconguis Isabelle I

eLife 20180925

The epithelial sodium channel (ENaC), a member of the ENaC/DEG superfamily, regulates Na<sup>+</sup> 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 w ...[more]

PMID: 30251954

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