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-Structure paper
| Title | Molecular principles of assembly, activation, and inhibition in epithelial sodium channel. |
|---|---|
| Journal, issue, pages | Elife, Vol. 9, Year 2020 |
| Publish date | Jul 30, 2020 |
 Authors | Sigrid Noreng / Richard Posert / Arpita Bharadwaj / Alexandra Houser / Isabelle Baconguis /  |
| PubMed 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 ...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 distinct regulatory sites: Na and the inhibitory peptide. Removal of the inhibitory peptide perturbs the Na site via the α2 helix highlighting the critical role of the α2 helix in regulating ENaC function. |
 External links | Elife / PubMed:32729833 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 3.06 Å |
| Structure data | EMDB-21896, PDB-6wth: |
| Chemicals |  ChemComp-NA:  ChemComp-NAG: |
| Source |
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 Keywords | MEMBRANE PROTEIN / sodium channel / blood pressure / epithelial / salt transport |
homo sapiens (human)
mus musculus (house mouse)