7s0f
Isoproterenol bound beta1 adrenergic receptor in complex with heterotrimeric Gi proteinIsoproterenol bound beta1 adrenergic receptor in complex with heterotrimeric Gi protein
Structural highlights
FunctionGBG2_BOVIN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Publication Abstract from PubMedThe beta(1)-adrenergic receptor (beta(1)-AR) can activate two families of G proteins. When coupled to Gs, beta(1)-AR increases cardiac output, and coupling to Gi leads to decreased responsiveness in myocardial infarction. By comparative structural analysis of turkey beta(1)-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 alpha5-helices on Galpha(i) and Galpha(s) interact similarly with beta(1)-AR, the overall interacting modes between beta(1)-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 beta(1)-AR is determined by the entire three-dimensional interaction surface, including intracellular loops 2 and 4 (ICL2 and ICL4). Structural basis and mechanism of activation of two different families of G proteins by the same GPCR.,Alegre KO, Paknejad N, Su M, Lou JS, Huang J, Jordan KD, Eng ET, Meyerson JR, Hite RK, Huang XY Nat Struct Mol Biol. 2021 Nov;28(11):936-944. doi: 10.1038/s41594-021-00679-2. , Epub 2021 Nov 10. PMID:34759376[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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