PREreviews of “Cryo-EM structure of cell-free synthesized human histamine H2receptor coupled to heterotrimeric Gsprotein in lipid nanodisc environment”

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Cryo-EM structure of cell-free synthesized human histamine H₂receptor coupled to heterotrimeric G_sprotein in lipid nanodisc environment

by Zoe Köck, Kilian Schnelle, Margherita Persechino, Simon Umbach, Hannes Schihada, Dovile Januliene, Kristian Parey, Steffen Pockes, Peter Kolb, Volker Dötsch, Arne Möller, Daniel Hilger, and Frank Bernhard

Posted: July 27, 2023
Server: bioRxiv
DOI: 10.1101/2023.07.27.550782

Abstract

Here we describe the cryo-electron microscopy structure of the human histamine 2 receptor (H₂R) in an active conformation with bound histamine and in complex with G_sheterotrimeric protein at an overall resolution of 3.4 Å. The complex was generated by cotranslational insertion into preformed nanodisc membranes using cell-free synthesis inE. colilysates. It is the first structure obtained by this detergent-free strategy and the first GPCR/G_scomplex structure in lipid environment. Structural comparison with the inactive conformation of H₂R and the inactive and G_q-coupled active state of H₁R 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 H₂R, its agonist-dependent internalization and its interaction with endogenously synthesized H₁R and H₂R in HEK293 cells by applying a recently developed nanotransfer technique.

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PREreview by Emelyne M. Pacull et al. of the Biophysics Leipzig University

Authored by Emelyne M. Pacull, Jeannette Laugwitz, and Matthias Voitel of the Biophysics Leipzig University

Summary of the paper:
In this paper, the authors report on the expression of the human histamine 2 receptor (H₂R) using the cell-free (CF) expression procedure with co-translational insertion into nanodiscs and formation of a complex with the endogenous ligand histamine, the Gs protein and the Gs…

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PREreviews of Cryo-EM structure of cell-free synthesized human histamine H2receptor coupled to heterotrimeric Gsprotein in lipid nanodisc environment

1 PREreview

PREreviews of Cryo-EM structure of cell-free synthesized human histamine H₂receptor coupled to heterotrimeric G_sprotein in lipid nanodisc environment