{"database":"biostudies-literature","file_versions":[],"scores":{"citationCount":0,"reanalysisCount":0,"viewCount":45,"searchCount":0},"additional":{"submitter":["Henault CM"],"funding":["NIGMS NIH HHS"],"pagination":["1156-1164"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8423587"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(12)"],"pubmed_abstract":["Phospholipids are key components of cellular membranes and are emerging as important functional regulators of different membrane proteins, including pentameric ligand-gated ion channels (pLGICs). Here, we take advantage of the prokaryote channel ELIC (Erwinia ligand-gated ion channel) as a model to understand the determinants of phospholipid interactions in this family of receptors. A high-resolution structure of ELIC in a lipid-bound state reveals a phospholipid site at the lower half of pore-forming transmembrane helices M1 and M4 and at a nearby site for neurosteroids, cholesterol or general anesthetics. This site is shaped by an M4-helix kink and a Trp-Arg-Pro triad that is highly conserved in eukaryote GABA<sub>A/C</sub> and glycine receptors. A combined approach reveals that M4 is intrinsically flexible and that M4 deletions or disruptions of the lipid-binding site accelerate desensitization in ELIC, suggesting that lipid interactions shape the agonist response. Our data offer a structural context for understanding lipid modulation in pLGICs."],"journal":["Nature chemical biology"],"pubmed_title":["A lipid site shapes the agonist response of a pentameric ligand-gated ion channel."],"pmcid":["PMC8423587"],"funding_grant_id":["R01 GM097159","P01 GM055876"],"pubmed_authors":["Lynch J","Steyaert J","Woods K","Baenziger JE","Cuello LG","Brams M","Evans GL","Govaerts C","Spurny R","Henault CM","Brannigan G","Elberson BW","Bertrand D","Nury H","Ulens C","Estrada-Mondragon A","Pardon E"],"view_count":["45"],"additional_accession":[]},"is_claimable":false,"name":"A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.","description":"Phospholipids are key components of cellular membranes and are emerging as important functional regulators of different membrane proteins, including pentameric ligand-gated ion channels (pLGICs). Here, we take advantage of the prokaryote channel ELIC (Erwinia ligand-gated ion channel) as a model to understand the determinants of phospholipid interactions in this family of receptors. A high-resolution structure of ELIC in a lipid-bound state reveals a phospholipid site at the lower half of pore-forming transmembrane helices M1 and M4 and at a nearby site for neurosteroids, cholesterol or general anesthetics. This site is shaped by an M4-helix kink and a Trp-Arg-Pro triad that is highly conserved in eukaryote GABA<sub>A/C</sub> and glycine receptors. A combined approach reveals that M4 is intrinsically flexible and that M4 deletions or disruptions of the lipid-binding site accelerate desensitization in ELIC, suggesting that lipid interactions shape the agonist response. Our data offer a structural context for understanding lipid modulation in pLGICs.","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Dec","modification":"2024-11-19T15:09:38.901Z","creation":"2022-02-11T10:52:07.262Z"},"accession":"S-EPMC8423587","cross_references":{"pubmed":["31591563"],"doi":["10.1038/s41589-019-0369-4"]}}