8g05 | pdb_00008g05

Cryo-EM structure of an orphan GPCR-Gi protein signaling complex

spinqualitylabelsall models 8g05, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8g05 is a 5 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 3Å Ligands: CLR, YI9 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GPR84_HUMAN Receptor for medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14. Capric acid (C10:0), undecanoic acid (C11:0) and lauric acid (C12:0) are the most potent agonists. Not activated by short-chain and long-chain saturated and unsaturated FFAs. Activation by medium-chain free fatty acid is coupled to a pertussis toxin sensitive G(i/o) protein pathway. May have important roles in processes from fatty acid metabolism to regulation of the immune system. Publication Abstract from PubMed GPR84 is a unique orphan G protein-coupled receptor (GPCR) that can be activated by endogenous medium-chain fatty acids (MCFAs). The signaling of GPR84 is largely pro-inflammatory, which can augment inflammatory response, and GPR84 also functions as a pro-phagocytic receptor to enhance phagocytic activities of macrophages. In this study, we show that the activation of GPR84 by the synthetic agonist 6-OAU can synergize with the blockade of CD47 on cancer cells to induce phagocytosis of cancer cells by macrophages. We also determine a high-resolution structure of the GPR84-G(i) signaling complex with 6-OAU. This structure reveals an occluded binding pocket for 6-OAU, the molecular basis of receptor activation involving non-conserved structural motifs of GPR84, and an unusual G(i)-coupling interface. Together with computational docking and simulations studies, this structure also suggests a mechanism for the high selectivity of GPR84 for MCFAs and a potential routes of ligand binding and dissociation. These results provide a framework for understanding GPR84 signaling and developing new drugs targeting GPR84. Pro-phagocytic function and structural basis of GPR84 signaling.,Zhang X, Wang Y, Supekar S, Cao X, Zhou J, Dang J, Chen S, Jenkins L, Marsango S, Li X, Liu G, Milligan G, Feng M, Fan H, Gong W, Zhang C Nat Commun. 2023 Sep 14;14(1):5706. doi: 10.1038/s41467-023-41201-0. PMID:37709767 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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