7jjo

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

spinqualitylabelsall models 7jjo, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7jjo is a 5 chain structure with sequence from Bos taurus, Lama glama and Meleagris gallopavo. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.6Å Ligands: 5FW Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_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 PubMed Cardiac disease remains the leading cause of morbidity and mortality worldwide. The beta1-adrenergic receptor (beta1-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 beta1-ARs, leading to increased heart rate and contractility. Here, we use cryo-electron microscopy and functional studies to investigate the molecular mechanism by which beta1-AR activates Gs. We find that the tilting of alpha5-helix breaks a hydrogen bond between the sidechain of His373 in the C-terminal alpha5-helix and the backbone carbonyl of Arg38 in the N-terminal alphaN-helix of Galphas. Together with the disruption of another interacting network involving Gln59 in the alpha1-helix, Ala352 in the beta6-alpha5 loop, and Thr355 in the alpha5-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. Structural Basis of the Activation of Heterotrimeric Gs-Protein by Isoproterenol-Bound beta1-Adrenergic Receptor.,Su M, Zhu L, Zhang Y, Paknejad N, Dey R, Huang J, Lee MY, Williams D, Jordan KD, Eng ET, Ernst OP, Meyerson JR, Hite RK, Walz T, Liu W, Huang XY Mol Cell. 2020 Oct 1;80(1):59-71.e4. doi: 10.1016/j.molcel.2020.08.001. Epub 2020, Aug 19. PMID:32818430 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Adrenergic receptor 3D structures Antibody 3D structures GTP-binding protein 3D structures Transducin 3D structures

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