8dcs | pdb_00008dcs

Cryo-EM structure of cyanopindolol-bound beta1-adrenergic receptor in complex with heterotrimeric Gs-protein

spinqualitylabelsall models 8dcs, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8dcs 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 2.5Å Ligands: P32 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 G-protein-coupled receptors (GPCRs) receive signals from ligands with different efficacies, and transduce to heterotrimeric G-proteins to generate different degrees of physiological responses. Previous studies revealed how ligands with different efficacies activate GPCRs. Here, we investigate how a GPCR activates G-proteins upon binding ligands with different efficacies. We report the cryo-EM structures of beta(1)-adrenergic receptor (beta(1)-AR) in complex with Gs (Galpha(s)Gbeta(1)Ggamma(2)) and a partial agonist or a very weak partial agonist, and compare them to the beta(1)-AR-Gs structure in complex with a full agonist. Analyses reveal similar overall complex architecture, with local conformational differences. Cellular functional studies with mutations of beta(1)-AR residues show effects on the cellular signaling from beta(1)-AR to the cAMP response initiated by the three different ligands, with residue-specific functional differences. Biochemical investigations uncover that the intermediate state complex comprising beta(1)-AR and nucleotide-free Gs is more stable when binding a full agonist than a partial agonist. Molecular dynamics simulations support the local conformational flexibilities and different stabilities among the three complexes. These data provide insights into the ligand efficacy in the activation of GPCRs and G-proteins. Structures of beta(1)-adrenergic receptor in complex with Gs and ligands of different efficacies.,Su M, Paknejad N, Zhu L, Wang J, Do HN, Miao Y, Liu W, Hite RK, Huang XY Nat Commun. 2022 Jul 14;13(1):4095. doi: 10.1038/s41467-022-31823-1. PMID:35835792 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Transducin 3D structures

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