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Publication Abstract from PubMed

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 alpha:beta:gamma 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.

Structure of the human epithelial sodium channel by cryo-electron microscopy.,Noreng S, Bharadwaj A, Posert R, Yoshioka C, Baconguis I Elife. 2018 Sep 25;7. pii: 39340. doi: 10.7554/eLife.39340. PMID:30251954^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.