title: The Structure of the Mouse Serotonin 5-HT3 Receptor in Lipid Vesicles.
abstract: The function of membrane proteins is best understood if their structure in the lipid membrane is known. Here, we determined the structure of the mouse serotonin 5-HT3 receptor inserted in lipid bilayers to a resolution of 12 Å without stabilizing antibodies by cryo electron tomography and subtomogram averaging. The reconstruction reveals protein secondary structure elements in the transmembrane region, the extracellular pore, and the transmembrane channel pathway, showing an overall similarity to the available X-ray model of the truncated 5-HT3 receptor determined in the presence of a stabilizing nanobody. Structural analysis of the 5-HT3 receptor embedded in a lipid bilayer allowed the position of the membrane to be determined. Interactions between the densely packed receptors in lipids were visualized, revealing that the interactions were maintained by the short horizontal helices. In combination with methodological improvements, our approach enables the structural analysis of membrane proteins in response to voltage and ligand gating.
authors.affiliation: Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, 4058 Basel, Switzerland; Focal Area Infection Biology, Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland. Electronic address: misha.kudryashev@biophys.mpg.de.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Kudryashev
authors.affiliation: Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, 4058 Basel, Switzerland; Scientific Computing Unit, Max Planck Institute for Brain Research, Max-von-Laue-Straße 4, 60438 Frankfurt am Main, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Castaño-Díez
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Institute of Chemical Sciences and Engineering (ISIC), Station 6, 1015 Lausanne, Switzerland.
authors.forename: Cédric
authors.initials: C
authors.lastname: Deluz
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Institute of Chemical Sciences and Engineering (ISIC), Station 6, 1015 Lausanne, Switzerland.
authors.forename: Gherici
authors.initials: G
authors.lastname: Hassaine
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Institute of Chemical Sciences and Engineering (ISIC), Station 6, 1015 Lausanne, Switzerland.
authors.forename: Luigino
authors.initials: L
authors.lastname: Grasso
authors.affiliation: Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Graf-Meyer
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne (EPFL), Institute of Chemical Sciences and Engineering (ISIC), Station 6, 1015 Lausanne, Switzerland. Electronic address: horst.vogel@epfl.ch.
authors.forename: Horst
authors.initials: H
authors.lastname: Vogel
authors.affiliation: Center for Cellular Imaging and NanoAnalytics (C-CINA), Biozentrum, University of Basel, Mattenstrasse 26, 4058 Basel, Switzerland.
authors.forename: Henning
authors.initials: H
authors.lastname: Stahlberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000737:chemistry; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry*
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D010743:Phospholipids; D044406:Receptors, Serotonin, 5-HT3