EMD-17793

Single-particle
3.4 Å
EMD-17793 Deposition: 05/07/2023
Map released: 06/03/2024
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-17793

Cryo-EM structure of cell-free synthesized human histamine H2 receptor coupled to heterotrimeric Gs protein in lipid environment

EMD-17793

Single-particle
3.4 Å
EMD-17793 Deposition: 05/07/2023
Map released: 06/03/2024
Last modified: 09/10/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Homo sapiens, Lama glama
Sample: H2 receptor coupled to heterotrimeric Gs protein
Fitted models: 8pok (Avg. Q-score: 0.501)

Deposition Authors: Schnelle K , Koeck Z, Persechino M , Umbach S, Schihada H, Januliene D , Parey K , Pockes S , Kolb P , Doetsch V, Moeller A, Hilger D , Bernhard F
Cryo-EM structure of cell-free synthesized human histamine 2 receptor/G s complex in nanodisc environment.
PUBMED: 38418462
DOI: doi:10.1038/s41467-024-46096-z
ISSN: 2041-1723
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 Gs 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 H2R and the inactive and Gq-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.