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4xt1

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Structure of a nanobody-bound viral GPCR bound to human chemokine CX3CL1

Structural highlights

4xt1 is a 3 chain structure with sequence from Cytomegalovirus, Homo sapiens and Vicugna pacos. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.886Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4xt1"

@@ Line 1: / Line 1: @@
 ==Structure of a nanobody-bound viral GPCR bound to human chemokine CX3CL1==
-<StructureSection load='4xt1' size='340' side='right' caption='[[4xt1]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
+<StructureSection load='4xt1' size='340' side='right'caption='[[4xt1]], [[Resolution|resolution]] 2.89&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4xt1]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XT1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XT1 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4xt1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Cytomegalovirus Cytomegalovirus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Vicugna_pacos Vicugna pacos]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XT1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XT1 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</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]] 2.886&#8491;</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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene>, <scene name='pdbligand=SIN:SUCCINIC+ACID'>SIN</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene></td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4xt3|4xt3]]</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=4xt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xt1 OCA], [https://pdbe.org/4xt1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xt1 RCSB], [https://www.ebi.ac.uk/pdbsum/4xt1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xt1 ProSAT]</span></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=4xt1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xt1 OCA], [http://pdbe.org/4xt1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xt1 RCSB], [http://www.ebi.ac.uk/pdbsum/4xt1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4xt1 ProSAT]</span></td></tr>
 </table>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Burg, J S]]
+[[Category: Cytomegalovirus]]
-[[Category: Garcia, K C]]
+[[Category: Homo sapiens]]
-[[Category: Jude, K M]]
+[[Category: Large Structures]]
-[[Category: Waghray, D]]
+[[Category: Vicugna pacos]]
-[[Category: Chemokine]]
+[[Category: Burg JS]]
-[[Category: Complex]]
+[[Category: Garcia KC]]
-[[Category: Gpcr]]
+[[Category: Jude KM]]
-[[Category: Membrane protein]]
+[[Category: Waghray D]]
-[[Category: Viral protein-signalling protein complex]]

4xt1

From Proteopedia

Current revision

Structure of a nanobody-bound viral GPCR bound to human chemokine CX3CL1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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