Structure of the human epithelial sodium channel by cryo-electron microscopy.
Elife
; 72018 09 25.
Article
em En
| MEDLINE
| ID: mdl-30251954
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 111 stoichiometry of αßγ 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.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sódio
/
Ativação do Canal Iônico
/
Microscopia Crioeletrônica
/
Canais Epiteliais de Sódio
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article