Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Nature communications, 2024-02, Vol.15 (1), p.1831-1831

Ort / Verlag

London: Nature Publishing Group

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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.The study describes the molecular structure of the human histamine 2 receptor in active conformation and in complex with Gs heterotrimer, synthesized in a cell-free system and co-translationally inserted into preformed nanodiscs.