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Title | Cryo-EM structure of cell-free synthesized human histamine 2 receptor/G complex in nanodisc environment. |
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Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 1831, Year 2024 |
Publish date | Feb 28, 2024 |
Authors | Zoe Köck / Kilian Schnelle / Margherita Persechino / Simon Umbach / Hannes Schihada / Dovile Januliene / Kristian Parey / Steffen Pockes / Peter Kolb / Volker Dötsch / Arne Möller / Daniel Hilger / Frank Bernhard / |
PubMed Abstract | Here we describe the cryo-electron microscopy structure of the human histamine 2 receptor (HR) in an active conformation with bound histamine and in complex with G heterotrimeric protein at an ...Here we describe the cryo-electron microscopy structure of the human histamine 2 receptor (HR) in an active conformation with bound histamine and in complex with G 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 HR and the inactive and G-coupled active state of HR 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 HR, its agonist-dependent internalization and its interaction with endogenously synthesized HR and HR in HEK293 cells by applying a recently developed nanotransfer technique. |
External links | Nat Commun / PubMed:38418462 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.4 Å |
Structure data | EMDB-17793, PDB-8pok: |
Chemicals | ChemComp-HSM: |
Source |
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Keywords | MEMBRANE PROTEIN / GPCR / Cell-free / H2R / human histamine 2 receptor / active conformation / complex / detergent-free / lipid environment |