7S0G

Isoproterenol bound beta1 adrenergic receptor in complex with heterotrimeric Gi/s chimera protein

Summary for 7S0G

• Entry DOI: 10.2210/pdb7s0g/pdb
• EMDB information: 24790
• Descriptor: Beta1-Adrenergic Receptor, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short chimera, ... (5 entities in total)
• Functional Keywords: chimera gi/s protein, gpcr-gi-s complex, agonist, signaling protein
• Biological source: Meleagris gallopavo; More
• Total number of polymer chains: 4
• Total formula weight: 146671.07

Authors

Paknejad, N.,Alegre, K.O.,Su, M.,Lou, J.S.,Huang, J.,Jordan, K.D.,Eng, E.T.,Meyerson, J.R.,Hite, R.K.,Huang, X.Y. (deposition date: 2021-08-30, release date: 2021-11-17, Last modification date: 2024-10-30)

Primary citation

Alegre, K.O.,Paknejad, N.,Su, M.,Lou, J.S.,Huang, J.,Jordan, K.D.,Eng, E.T.,Meyerson, J.R.,Hite, R.K.,Huang, X.Y.
Structural basis and mechanism of activation of two different families of G proteins by the same GPCR.
Nat.Struct.Mol.Biol., 28:936-944, 2021

PubMed Abstract: The β-adrenergic receptor (β-AR) can activate two families of G proteins. When coupled to Gs, β-AR increases cardiac output, and coupling to Gi leads to decreased responsiveness in myocardial infarction. By comparative structural analysis of turkey β-AR complexed with either Gi or Gs, we investigate how a single G-protein-coupled receptor simultaneously signals through two G proteins. We find that, although the critical receptor-interacting C-terminal α5-helices on Gα and Gα interact similarly with β-AR, the overall interacting modes between β-AR and G proteins vary substantially. Functional studies reveal the importance of the differing interactions and provide evidence that the activation efficacy of G proteins by β-AR is determined by the entire three-dimensional interaction surface, including intracellular loops 2 and 4 (ICL2 and ICL4).

PubMed: 34759376
DOI: 10.1038/s41594-021-00679-2

Experimental method

ELECTRON MICROSCOPY (3.86 Å)