8g05

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'''Unreleased structure'''
 
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The entry 8g05 is ON HOLD
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==Cryo-EM structure of an orphan GPCR-Gi protein signaling complex==
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<StructureSection load='8g05' size='340' side='right'caption='[[8g05]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[8g05]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G05 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G05 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=YI9:6-(octylamino)-5~{H}-pyrimidine-2,4-dione'>YI9</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8g05 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g05 OCA], [https://pdbe.org/8g05 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g05 RCSB], [https://www.ebi.ac.uk/pdbsum/8g05 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g05 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GPR84_HUMAN GPR84_HUMAN] G protein-coupled receptor that responds endogenously to dietary fatty acids or nutrient, specifically 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 (PubMed:16966319). In immune cells, functions as a pro-inflammatory receptor via 6-OAU and promotes the expression of pro-inflammatory mediators such as TNFalpha, IL-6 and IL-12B as well as stimulating chemotactic responses through activation of signaling mediators AKT, ERK and NF-kappa-B (By similarity). In addition, triggers increased bacterial adhesion and phagocytosis in macrophages and regulates pro-inflammatory function via enhancing NLRP3 inflammasome activation (By similarity). Plays also an important role in inflammation by modulating neutrophil functions (By similarity). Mechanistically, promotes neutrophil chemotaxis, reactive oxygen species (ROS) production and degranulation via LYN-AKT/ERK pathway (By similarity). To regulate ROS, communicates with the two formyl peptide receptors FPR2 and FPR1 to control the NADPH oxidase activity in neutrophils (PubMed:33789297).[UniProtKB:Q8CIM5]<ref>PMID:16966319</ref> <ref>PMID:33789297</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors: Zhang, X., Wang, Y.J., Li, X., Liu, G.B., Gong, W.M., Zhang, C.
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, PMID:37709767<ref>PMID:37709767</ref>
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Description: Cryo-EM structure of an orphan GPCR-Gi protein signaling complex
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Gong, W.M]]
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<div class="pdbe-citations 8g05" style="background-color:#fffaf0;"></div>
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[[Category: Li, X]]
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== References ==
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[[Category: Zhang, X]]
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<references/>
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[[Category: Liu, G.B]]
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__TOC__
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[[Category: Wang, Y.J]]
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</StructureSection>
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[[Category: Zhang, C]]
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Gong WM]]
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[[Category: Li X]]
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[[Category: Liu GB]]
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[[Category: Wang YJ]]
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[[Category: Zhang C]]
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[[Category: Zhang X]]

Current revision

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

PDB ID 8g05

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