{"doi":"10.7554/elife.59038","title":"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 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.","journal":"eLife","year":2020,"id":58519,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":72,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307033,"name":"Richard Posert","orcid":"0000-0001-9010-2104","position":1,"is_corresponding":false},{"id":307034,"name":"Arpita Bharadwaj","orcid":"0000-0002-3867-7610","position":2,"is_corresponding":false},{"id":307035,"name":"Alexandra Houser","orcid":"0000-0001-5516-6225","position":3,"is_corresponding":false},{"id":307036,"name":"Isabelle Baconguis","orcid":"0000-0002-5440-2289","position":4,"is_corresponding":false},{"id":307032,"name":"Sigrid Noreng","orcid":"0000-0001-5767-1399","position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-18T21:07:33.416320Z","pmid":"32729833","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}