8jpb | pdb_00008jpb

cryo-EM structure of NTSR1-GRK2-Galpha(q) complexes 1

spinqualitylabelsall models 8jpb, resolution 3.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8jpb is a 4 chain structure with sequence from Bos taurus, Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.07Å Ligands: ALF, GDP, MG, SRW, STU Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ARBK1_BOVIN Specifically phosphorylates the agonist-occupied form of the beta-adrenergic and closely related receptors, probably inducing a desensitization of them. Key regulator of LPAR1 signaling. Competes with RALA for binding to LPAR1 thus affecting the signaling properties of the receptor. Desensitizes LPAR1 and LPAR2 in a phosphorylation-independent manner (By similarity). Publication Abstract from PubMed Phosphorylation of G-protein-coupled receptors (GPCRs) by GPCR kinases (GRKs) desensitizes G-protein signalling and promotes arrestin signalling, which is also modulated by biased ligands(1-6). The molecular assembly of GRKs on GPCRs and the basis of GRK-mediated biased signalling remain largely unknown owing to the weak GPCR-GRK interactions. Here we report the complex structure of neurotensin receptor 1 (NTSR1) bound to GRK2, Galpha(q) and the arrestin-biased ligand SBI-553(7). The density map reveals the arrangement of the intact GRK2 with the receptor, with the N-terminal helix of GRK2 docking into the open cytoplasmic pocket formed by the outward movement of the receptor transmembrane helix 6, analogous to the binding of the G protein to the receptor. SBI-553 binds at the interface between GRK2 and NTSR1 to enhance GRK2 binding. The binding mode of SBI-553 is compatible with arrestin binding but clashes with the binding of Galpha(q) protein, thus providing a mechanism for its arrestin-biased signalling capability. In sum, our structure provides a rational model for understanding the details of GPCR-GRK interactions and GRK2-mediated biased signalling. GPCR activation and GRK2 assembly by a biased intracellular agonist.,Duan J, Liu H, Zhao F, Yuan Q, Ji Y, Cai X, He X, Li X, Li J, Wu K, Gao T, Zhu S, Lin S, Wang MW, Cheng X, Yin W, Jiang Y, Yang D, Xu HE Nature. 2023 Aug;620(7974):676-681. doi: 10.1038/s41586-023-06395-9. Epub 2023 , Aug 2. PMID:37532940 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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