8POK

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

8POK の概要

• エントリーDOI: 10.2210/pdb8pok/pdb
• EMDBエントリー: 17793
• 分子名称: Histamine H2 receptor, Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (6 entities in total)
• 機能のキーワード: gpcr, cell-free, h2r, human histamine 2 receptor, active conformation, complex, detergent-free, lipid environment, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 146866.99

構造登録者

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. (登録日: 2023-07-05, 公開日: 2024-03-06, 最終更新日: 2024-10-09)

主引用文献

Kock, Z.,Schnelle, K.,Persechino, M.,Umbach, S.,Schihada, H.,Januliene, D.,Parey, K.,Pockes, S.,Kolb, P.,Dotsch, V.,Moller, A.,Hilger, D.,Bernhard, F.
Cryo-EM structure of cell-free synthesized human histamine 2 receptor/G s complex in nanodisc environment.
Nat Commun, 15:1831-1831, 2024

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 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.

PubMed: 38418462
DOI: 10.1038/s41467-024-46096-z

実験手法

ELECTRON MICROSCOPY (3.4 Å)