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A lipid site shapes the agonist response of a pentameric ligand-gated ion channel.
Hénault, Camille M; Govaerts, Cedric; Spurny, Radovan; Brams, Marijke; Estrada-Mondragon, Argel; Lynch, Joseph; Bertrand, Daniel; Pardon, Els; Evans, Genevieve L; Woods, Kristen; Elberson, Benjamin W; Cuello, Luis G; Brannigan, Grace; Nury, Hugues; Steyaert, Jan; Baenziger, John E; Ulens, Chris.
Affiliation
  • Hénault CM; Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
  • Govaerts C; Laboratory for the Structure and Function of Biological Membranes, Center for Structural Biology and Bioinformatics, Université libre de Bruxelles, Brussels, Belgium.
  • Spurny R; Laboratory of Structural Neurobiology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
  • Brams M; Laboratory of Structural Neurobiology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
  • Estrada-Mondragon A; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Lynch J; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Bertrand D; HiQscreen, Vésenaz, Geneva, Switzerland.
  • Pardon E; Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium.
  • Evans GL; VIB-VUB Center for Structural Biology, VIB, Brussels, Belgium.
  • Woods K; Laboratory of Structural Neurobiology, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
  • Elberson BW; Center for Computational and Integrative Biology, Rutgers University-Camden, Camden, NJ, USA.
  • Cuello LG; Department of Physics, Rutgers University-Camden, Camden, NJ, USA.
  • Brannigan G; Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, TTUHSC, Lubbock, TX, USA.
  • Nury H; Department of Cell Physiology and Molecular Biophysics, Center for Membrane Protein Research, TTUHSC, Lubbock, TX, USA.
  • Steyaert J; Center for Computational and Integrative Biology, Rutgers University-Camden, Camden, NJ, USA.
  • Baenziger JE; Department of Physics, Rutgers University-Camden, Camden, NJ, USA.
  • Ulens C; University Grenoble Alpes, CNRS, IBS, Grenoble, France.
Nat Chem Biol ; 15(12): 1156-1164, 2019 12.
Article de En | MEDLINE | ID: mdl-31591563
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 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.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Ouverture et fermeture des portes des canaux ioniques / Canaux ioniques / Lipides Limites: Animals Langue: En Journal: Nat Chem Biol Sujet du journal: BIOLOGIA / QUIMICA Année: 2019 Type de document: Article Pays d'affiliation: Canada

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Ouverture et fermeture des portes des canaux ioniques / Canaux ioniques / Lipides Limites: Animals Langue: En Journal: Nat Chem Biol Sujet du journal: BIOLOGIA / QUIMICA Année: 2019 Type de document: Article Pays d'affiliation: Canada