6bqn
From Proteopedia
Cryo-EM structure of ENaC
Structural highlights
DiseaseSCNNA_HUMAN Idiopathic bronchiectasis;Generalized pseudohypoaldosteronism type 1. The disease is caused by mutations affecting the gene represented in this entry. The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty (PubMed:18634878). The disease is caused by mutations affecting the gene represented in this entry. FunctionSCNNA_HUMAN Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception. Publication Abstract from PubMedThe 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. Loading citation details.. Citations No citations found See AlsoReferences
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