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The Structure of the Mouse Serotonin 5-HT3 Receptor in Lipid Vesicles.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2016
Author Kudryashev Mikhail, Castaño-Díez Daniel, Deluz Cédric, Hassaine Gherici, Grasso Luigino, Graf-Meyer Alexandra, Vogel Horst, Stahlberg Henning,
Project Software for Electron Microscopy of Membrane Proteins
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Original article (peer-reviewed)

Journal Structure (London, England : 1993)
Volume (Issue) 24(1)
Page(s) 165 - 70
Title of proceedings Structure (London, England : 1993)
DOI 10.1016/j.str.2015.11.004

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.
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