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TitleStructural basis and mechanism of activation of two different families of G proteins by the same GPCR.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 11, Page 936-944, Year 2021
Publish dateNov 10, 2021
AuthorsKamela O Alegre / Navid Paknejad / Minfei Su / Jian-Shu Lou / Jianyun Huang / Kelsey D Jordan / Edward T Eng / Joel R Meyerson / Richard K Hite / Xin-Yun Huang /
PubMed AbstractThe 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 ...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).
External linksNat Struct Mol Biol / PubMed:34759376 / PubMed Central
MethodsEM (single particle)
Resolution2.96 - 3.86 Å
Structure data

EMDB-24789, PDB-7s0f:
Isoproterenol bound beta1 adrenergic receptor in complex with heterotrimeric Gi protein
Method: EM (single particle) / Resolution: 2.96 Å

EMDB-24790, PDB-7s0g:
Isoproterenol bound beta1 adrenergic receptor in complex with heterotrimeric Gi/s chimera protein
Method: EM (single particle) / Resolution: 3.86 Å

Chemicals

ChemComp-5FW:
ISOPRENALINE / medication*YM

Source
  • bos taurus (cattle)
  • meleagris gallopavo (turkey)
  • rattus norvegicus (Norway rat)
KeywordsSIGNALING PROTEIN / Gi protein / GPCR-Gi complex / agonist / chimera Gi/s protein / GPCR-Gi-s complex

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