6WTH

Full-length human ENaC ECD

Summary for 6WTH

• Entry DOI: 10.2210/pdb6wth/pdb
• EMDB information: 21896
• Descriptor: Amiloride-sensitive sodium channel subunit alpha, Amiloride-sensitive sodium channel subunit beta, Amiloride-sensitive sodium channel subunit gamma, ... (8 entities in total)
• Functional Keywords: sodium channel, blood pressure, epithelial, salt transport, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 7
• Total formula weight: 264774.37

Authors

Posert, R.,Baconguis, I.,Noreng, S.,Bharadwaj, A.,Houser, A. (deposition date: 2020-05-02, release date: 2020-08-12, Last modification date: 2024-10-23)

Primary citation

Noreng, S.,Posert, R.,Bharadwaj, A.,Houser, A.,Baconguis, I.
Molecular principles of assembly, activation, and inhibition in epithelial sodium channel.
Elife, 9:-, 2020

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 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.

PubMed: 32729833
DOI: 10.7554/eLife.59038

Experimental method

ELECTRON MICROSCOPY (3.06 Å)