8jpe | pdb_00008jpe

Focused refinement structure of Galpha(q) in NTSR1-GRK2-Galpha(q) complexes

spinqualitylabelsall models 8jpe, resolution 2.91Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8jpe is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.91Å Ligands: ALF, GDP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease GNAQ_HUMAN Sturge-Weber syndrome;Phakomatosis cesioflammea;Uveal melanoma;Familial multiple nevi flammei. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function GNAQ_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Regulates B-cell selection and survival and is required to prevent B-cell-dependent autoimmunity. Regulates chemotaxis of BM-derived neutrophils and dendritic cells (in vitro) (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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