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| | <StructureSection load='4xt3' size='340' side='right'caption='[[4xt3]], [[Resolution|resolution]] 3.80Å' scene=''> | | <StructureSection load='4xt3' size='340' side='right'caption='[[4xt3]], [[Resolution|resolution]] 3.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xt3]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Cytomegalovirus Cytomegalovirus] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XT3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XT3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xt3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Cytomegalovirus Cytomegalovirus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XT3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XT3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.801Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xt1|4xt1]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4xt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xt3 OCA], [https://pdbe.org/4xt3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xt3 RCSB], [https://www.ebi.ac.uk/pdbsum/4xt3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xt3 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CX3CL1, FKN, NTT, SCYD1, A-152E5.2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4xt3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xt3 OCA], [http://pdbe.org/4xt3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xt3 RCSB], [http://www.ebi.ac.uk/pdbsum/4xt3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xt3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/US28_HCMVA US28_HCMVA]] Receptor for a C-C type chemokine. Binds to a number of different CC-chemokines including CCL5/RANTES, CCL2/MCP-1, CCL3/MIP-1-alpha as well as CX3CL1/Fractalkine. Transduces signals resulting in the activation of MAP kinase signaling pathways and augmentation of intracellular calcium ion levels, leading to alterations in chemotactic behavior of vascular smooth muscle cells and macrophages. The US28 receptor also exhibits high levels of agonist-independent signaling activity and agonist-independent endocytosis. Interacts with endogenous Gaq/11 subunits and thereby constitutively activates phospholipase C.<ref>PMID:11050102</ref> <ref>PMID:7961796</ref> [[http://www.uniprot.org/uniprot/X3CL1_HUMAN X3CL1_HUMAN]] The soluble form is chemotactic for T-cells and monocytes, but not for neutrophils. The membrane-bound form promotes adhesion of those leukocytes to endothelial cells. May play a role in regulating leukocyte adhesion and migration processes at the endothelium. Binds to CX3CR1.<ref>PMID:21829356</ref> | + | [https://www.uniprot.org/uniprot/US28_HCMVA US28_HCMVA] Receptor for a C-C type chemokine. Binds to a number of different CC-chemokines including CCL5/RANTES, CCL2/MCP-1, CCL3/MIP-1-alpha as well as CX3CL1/Fractalkine. Transduces signals resulting in the activation of MAP kinase signaling pathways and augmentation of intracellular calcium ion levels, leading to alterations in chemotactic behavior of vascular smooth muscle cells and macrophages. The US28 receptor also exhibits high levels of agonist-independent signaling activity and agonist-independent endocytosis. Interacts with endogenous Gaq/11 subunits and thereby constitutively activates phospholipase C.<ref>PMID:11050102</ref> <ref>PMID:7961796</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Cytomegalovirus]] | | [[Category: Cytomegalovirus]] |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Burg, J S]] | + | [[Category: Burg JS]] |
| - | [[Category: Garcia, K C]] | + | [[Category: Garcia KC]] |
| - | [[Category: Jude, K M]] | + | [[Category: Jude KM]] |
| - | [[Category: Waghray, D]] | + | [[Category: Waghray D]] |
| - | [[Category: Chemokine]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Gpcr]]
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| - | [[Category: Membrane protein]]
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| - | [[Category: Viral protein-cytokine complex]]
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| - | [[Category: Viral protein-signalling protein complex]]
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| Structural highlights
Function
US28_HCMVA Receptor for a C-C type chemokine. Binds to a number of different CC-chemokines including CCL5/RANTES, CCL2/MCP-1, CCL3/MIP-1-alpha as well as CX3CL1/Fractalkine. Transduces signals resulting in the activation of MAP kinase signaling pathways and augmentation of intracellular calcium ion levels, leading to alterations in chemotactic behavior of vascular smooth muscle cells and macrophages. The US28 receptor also exhibits high levels of agonist-independent signaling activity and agonist-independent endocytosis. Interacts with endogenous Gaq/11 subunits and thereby constitutively activates phospholipase C.[1] [2]
Publication Abstract from PubMed
Chemokines are small proteins that function as immune modulators through activation of chemokine G protein-coupled receptors (GPCRs). Several viruses also encode chemokines and chemokine receptors to subvert the host immune response. How protein ligands activate GPCRs remains unknown. We report the crystal structure at 2.9 angstrom resolution of the human cytomegalovirus GPCR US28 in complex with the chemokine domain of human CX3CL1 (fractalkine). The globular body of CX3CL1 is perched on top of the US28 extracellular vestibule, whereas its amino terminus projects into the central core of US28. The transmembrane helices of US28 adopt an active-state-like conformation. Atomic-level simulations suggest that the agonist-independent activity of US28 may be due to an amino acid network evolved in the viral GPCR to destabilize the receptor's inactive state.
Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor.,Burg JS, Ingram JR, Venkatakrishnan AJ, Jude KM, Dukkipati A, Feinberg EN, Angelini A, Waghray D, Dror RO, Ploegh HL, Garcia KC Science. 2015 Mar 6;347(6226):1113-7. doi: 10.1126/science.aaa5026. PMID:25745166[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Casarosa P, Bakker RA, Verzijl D, Navis M, Timmerman H, Leurs R, Smit MJ. Constitutive signaling of the human cytomegalovirus-encoded chemokine receptor US28. J Biol Chem. 2001 Jan 12;276(2):1133-7. PMID:11050102 doi:http://dx.doi.org/10.1074/jbc.M008965200
- ↑ Gao JL, Murphy PM. Human cytomegalovirus open reading frame US28 encodes a functional beta chemokine receptor. J Biol Chem. 1994 Nov 18;269(46):28539-42. PMID:7961796
- ↑ Burg JS, Ingram JR, Venkatakrishnan AJ, Jude KM, Dukkipati A, Feinberg EN, Angelini A, Waghray D, Dror RO, Ploegh HL, Garcia KC. Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor. Science. 2015 Mar 6;347(6226):1113-7. doi: 10.1126/science.aaa5026. PMID:25745166 doi:http://dx.doi.org/10.1126/science.aaa5026
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