Molecular principles of assembly, activation, and inhibition in epithelial sodium channel.

ABSTRACT: The molecular bases of heteromeric assembly and link between Na⁺ self-inhibition and protease-sensitivity in epithelial sodium channels (ENaCs) are not fully understood. Previously, we demonstrated that ENaC subunits - α, β, and γ - assemble in a counterclockwise configuration when viewed from outside the cell with the protease-sensitive GRIP domains in the periphery (Noreng et al., 2018). Here we describe the structure of ENaC resolved by cryo-electron microscopy at 3 Å. We find that a combination of precise domain arrangement and complementary hydrogen bonding network defines the subunit arrangement. Furthermore, we determined that the α subunit has a primary functional module consisting of the finger and GRIP domains. The module is bifurcated by the α2 helix dividing two dist

SUBMITTER: Noreng S 

PROVIDER: S-EPMC7413742 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature