Cryo-EM structure of cell-free synthesized human histamine 2 receptor/G s complex in nanodisc environment.

Autor: Köck Z; Centre for Biomolecular Magnetic Resonance, Institute for Biophysical Chemistry, Goethe-University of Frankfurt/Main, Frankfurt, Germany., Schnelle K; Department of Biology/Chemistry, Structural Biology section, University of Osnabrück, Osnabrück, Germany.; Center of Cellular Nanoanalytic Osnabrück (CellNanOs), University of Osnabrück, Osnabrück, Germany., Persechino M; Department of Pharmaceutical Chemistry, University of Marburg, Marburg, Germany., Umbach S; Centre for Biomolecular Magnetic Resonance, Institute for Biophysical Chemistry, Goethe-University of Frankfurt/Main, Frankfurt, Germany., Schihada H; Department of Pharmaceutical Chemistry, University of Marburg, Marburg, Germany., Januliene D; Department of Biology/Chemistry, Structural Biology section, University of Osnabrück, Osnabrück, Germany.; Center of Cellular Nanoanalytic Osnabrück (CellNanOs), University of Osnabrück, Osnabrück, Germany., Parey K; Department of Biology/Chemistry, Structural Biology section, University of Osnabrück, Osnabrück, Germany.; Center of Cellular Nanoanalytic Osnabrück (CellNanOs), University of Osnabrück, Osnabrück, Germany., Pockes S; Institute of Pharmacy, University of Regensburg, Regensburg, Germany., Kolb P; Department of Pharmaceutical Chemistry, University of Marburg, Marburg, Germany., Dötsch V; Centre for Biomolecular Magnetic Resonance, Institute for Biophysical Chemistry, Goethe-University of Frankfurt/Main, Frankfurt, Germany., Möller A; Department of Biology/Chemistry, Structural Biology section, University of Osnabrück, Osnabrück, Germany. arne.moeller@uni-osnabrueck.de.; Center of Cellular Nanoanalytic Osnabrück (CellNanOs), University of Osnabrück, Osnabrück, Germany. arne.moeller@uni-osnabrueck.de., Hilger D; Department of Pharmaceutical Chemistry, University of Marburg, Marburg, Germany. daniel.hilger@pharmazie.uni-marburg.de., Bernhard F; Centre for Biomolecular Magnetic Resonance, Institute for Biophysical Chemistry, Goethe-University of Frankfurt/Main, Frankfurt, Germany. fbern@bpc.uni-frankfurt.de.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Feb 28; Vol. 15 (1), pp. 1831. Date of Electronic Publication: 2024 Feb 28.
DOI: 10.1038/s41467-024-46096-z
Abstrakt: Here we describe the cryo-electron microscopy structure of the human histamine 2 receptor (H 2 R) in an active conformation with bound histamine and in complex with G s heterotrimeric protein at an overall resolution of 3.4 Å. The complex was generated by cotranslational insertion of the receptor into preformed nanodisc membranes using cell-free synthesis in E. coli lysates. Structural comparison with the inactive conformation of H 2 R and the inactive and G q -coupled active state of H 1 R together with structure-guided functional experiments reveal molecular insights into the specificity of ligand binding and G protein coupling for this receptor family. We demonstrate lipid-modulated folding of cell-free synthesized H 2 R, its agonist-dependent internalization and its interaction with endogenously synthesized H 1 R and H 2 R in HEK293 cells by applying a recently developed nanotransfer technique.
(© 2024. The Author(s).)
Databáze: MEDLINE
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