Journal
ELIFE
Volume 9, Issue -, Pages -Publisher
eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.59038
Keywords
-
Categories
Funding
- National Institutes of Health [DP5OD017871, 19TPA34760754, 18PRE33990205, DGE-1937961]
Ask authors/readers for more resources
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 - alpha, beta, and gamma- 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 angstrom. We find that a combination of precise domain arrangement and complementary hydrogen bonding network defines the subunit arrangement. Furthermore, we determined that the a subunit has a primary functional module consisting of the finger and GRIP domains. The module is bifurcated by the alpha 2 helix dividing two distinct regulatory sites: Na+ and the inhibitory peptide. Removal of the inhibitory peptide perturbs the Na+ site via the alpha 2 helix highlighting the critical role of the alpha 2 helix in regulating ENaC function.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available