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TitleStructural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound β-Adrenergic Receptor.
Journal, issue, pagesMol Cell, Vol. 80, Issue 1, Page 59-71.e4, Year 2020
Publish dateOct 1, 2020
AuthorsMinfei Su / Lan Zhu / Yixiao Zhang / Navid Paknejad / Raja Dey / Jianyun Huang / Ming-Yue Lee / Dewight Williams / Kelsey D Jordan / Edward T Eng / Oliver P Ernst / Joel R Meyerson / Richard K Hite / Thomas Walz / Wei Liu / Xin-Yun Huang /
PubMed AbstractCardiac disease remains the leading cause of morbidity and mortality worldwide. The β-adrenergic receptor (β-AR) is a major regulator of cardiac functions and is downregulated in the majority of ...Cardiac disease remains the leading cause of morbidity and mortality worldwide. The β-adrenergic receptor (β-AR) is a major regulator of cardiac functions and is downregulated in the majority of heart failure cases. A key physiological process is the activation of heterotrimeric G-protein Gs by β-ARs, leading to increased heart rate and contractility. Here, we use cryo-electron microscopy and functional studies to investigate the molecular mechanism by which β-AR activates Gs. We find that the tilting of α5-helix breaks a hydrogen bond between the sidechain of His373 in the C-terminal α5-helix and the backbone carbonyl of Arg38 in the N-terminal αN-helix of Gα. Together with the disruption of another interacting network involving Gln59 in the α1-helix, Ala352 in the β6-α5 loop, and Thr355 in the α5-helix, these conformational changes might lead to the deformation of the GDP-binding pocket. Our data provide molecular insights into the activation of G-proteins by G-protein-coupled receptors.
External linksMol Cell / PubMed:32818430 / PubMed Central
MethodsEM (single particle)
Resolution2.6 Å
Structure data

22357

7jjo

EMDB-22357, PDB-7jjo:
Structural Basis of the Activation of Heterotrimeric Gs-protein by Isoproterenol-bound Beta1-Adrenergic Receptor
Method: EM (single particle) / Resolution: 2.6 Å

Chemicals

ChemComp-5FW:
ISOPRENALINE / medication, agonist*YM

Source
  • bos taurus (cattle)
  • lama glama (llama)
  • meleagris gallopavo (turkey)
KeywordsSIGNALING PROTEIN / Gs protein / GPCR-Gs complex / Agonist

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