par Hénault, Camille C.M.;Govaerts, Cédric ;Spurny, Radovan;Brams, Marijke;Estrada-Mondragon, Argel;Lynch, Joseph;Bertrand, Daniel;Pardon, Els;Evans, Genevieve G.L.;Woods, Kristen;Elberson, Benjamin Wallace;Cuello, Luis G;Brannigan, Grace;Nury, Hugues;Steyaert, Jan;Baenziger, John J.E.;Ulens, Chris
Référence Nature Chemical Biology, 15, 12, page (1156-1164)
Publication Publié, 2019-12-01
Référence Nature Chemical Biology, 15, 12, page (1156-1164)
Publication Publié, 2019-12-01
Article révisé par les pairs
Résumé : | 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 GABAA/C 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. |