7JJO

Structural Basis of the Activation of Heterotrimeric Gs-protein by Isoproterenol-bound Beta1-Adrenergic Receptor

Summary for 7JJO

• Entry DOI: 10.2210/pdb7jjo/pdb
• EMDB information: 22357
• Descriptor: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Nanobody 35, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, ... (6 entities in total)
• Functional Keywords: gs protein, gpcr-gs complex, agonist, signaling protein
• Biological source: Bos taurus (Bovine); More
• Total number of polymer chains: 5
• Total formula weight: 163136.03

Authors

Su, M.,Zhu, L.,Zhang, Y.,Paknejad, N.,Dey, R.,Huang, J.,Lee, M.Y.,Williams, D.,Jordan, K.D.,Eng, E.T.,Ernst, O.P.,Meyerson, J.R.,Hite, R.K.,Walz, T.,Liu, W.,Huang, X.Y. (deposition date: 2020-07-27, release date: 2020-09-02, Last modification date: 2024-11-20)

Primary citation

Su, M.,Zhu, L.,Zhang, Y.,Paknejad, N.,Dey, R.,Huang, J.,Lee, M.Y.,Williams, D.,Jordan, K.D.,Eng, E.T.,Ernst, O.P.,Meyerson, J.R.,Hite, R.K.,Walz, T.,Liu, W.,Huang, X.Y.
Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound beta 1 -Adrenergic Receptor.
Mol.Cell, 80:59-, 2020

PubMed Abstract: 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.

PubMed: 32818430
DOI: 10.1016/j.molcel.2020.08.001

Experimental method

ELECTRON MICROSCOPY (2.6 Å)