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2k04

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==Structure of SDF1 in complex with the CXCR4 N-terminus containing no sulfotyrosines==
==Structure of SDF1 in complex with the CXCR4 N-terminus containing no sulfotyrosines==
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<StructureSection load='2k04' size='340' side='right' caption='[[2k04]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
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<StructureSection load='2k04' size='340' side='right'caption='[[2k04]]' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2k04]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K04 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2K04 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2k04]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K04 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K04 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2k01|2k01]], [[2k03|2k03]], [[2k05|2k05]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CXCL12, SDF1, SDF1A, SDF1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), CXCR4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=2k04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k04 OCA], [https://pdbe.org/2k04 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k04 RCSB], [https://www.ebi.ac.uk/pdbsum/2k04 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k04 ProSAT]</span></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2k04 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k04 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2k04 RCSB], [http://www.ebi.ac.uk/pdbsum/2k04 PDBsum]</span></td></tr>
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</table>
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<table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/CXCR4_HUMAN CXCR4_HUMAN]] Defects in CXCR4 are a cause of WHIM syndrome (WHIM) [MIM:[http://omim.org/entry/193670 193670]]; also known as warts, hypogammaglobulinemia, infections and myelokathexis. WHIM syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis.<ref>PMID:12692554</ref>
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== Function ==
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[[http://www.uniprot.org/uniprot/SDF1_HUMAN SDF1_HUMAN]] Chemoattractant active on T-lymphocytes, monocytes, but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to another C-X-C chemokine receptor CXCR7, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and CXCR7, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of CXCR7 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation.<ref>PMID:8752281</ref> <ref>PMID:11069075</ref> <ref>PMID:11859124</ref> <ref>PMID:16107333</ref> <ref>PMID:18802065</ref> <ref>PMID:19255243</ref> [[http://www.uniprot.org/uniprot/CXCR4_HUMAN CXCR4_HUMAN]] Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading to enhanced intracellular calcium ions and reduced cellular cAMP levels. Involved in hematopoiesis and in cardiac ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract, probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in cerebellar development. In the CNS, could mediate hippocampal-neuron survival. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus.<ref>PMID:8329116</ref> <ref>PMID:8234909</ref> <ref>PMID:8629022</ref> <ref>PMID:8752280</ref> <ref>PMID:8752281</ref> <ref>PMID:10074102</ref> <ref>PMID:10644702</ref> <ref>PMID:10825158</ref> <ref>PMID:17197449</ref> <ref>PMID:20048153</ref> <ref>PMID:20228059</ref> <ref>PMID:20505072</ref>
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== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
Check<jmol>
<jmolCheckbox>
<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k0/2k04_consurf.spt"</scriptWhenChecked>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k0/2k04_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
<text>to colour the structure by Evolutionary Conservation</text>
<text>to colour the structure by Evolutionary Conservation</text>
</jmolCheckbox>
</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2k04 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
</div>
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<div class="pdbe-citations 2k04" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[C-X-C motif chemokine|C-X-C motif chemokine]]
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*[[C-X-C motif chemokine 3D structures|C-X-C motif chemokine 3D structures]]
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*[[CXC chemokine receptor|CXC chemokine receptor]]
*[[CXC chemokine receptor type 4|CXC chemokine receptor type 4]]
*[[CXC chemokine receptor type 4|CXC chemokine receptor type 4]]
*[[Stromal Derived Factor 1|Stromal Derived Factor 1]]
*[[Stromal Derived Factor 1|Stromal Derived Factor 1]]
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</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Peterson, F C.]]
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[[Category: Large Structures]]
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[[Category: Veldkamp, C T.]]
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[[Category: Peterson FC]]
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[[Category: Volkman, B F.]]
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[[Category: Veldkamp CT]]
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[[Category: Chemokine]]
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[[Category: Volkman BF]]
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[[Category: Chemotaxis]]
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[[Category: Cxcl12]]
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[[Category: Cxcr4]]
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[[Category: Cytokine]]
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[[Category: G-protein coupled receptor]]
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[[Category: Glycoprotein]]
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[[Category: Growth factor]]
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[[Category: Host-virus interaction]]
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[[Category: Locked dimer]]
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[[Category: Membrane]]
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[[Category: Receptor]]
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[[Category: Sdf1-alpha]]
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[[Category: Secreted]]
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[[Category: Stromal cell derived factor-1]]
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[[Category: Sulfation]]
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[[Category: Transducer]]
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[[Category: Transmembrane]]
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Current revision

Structure of SDF1 in complex with the CXCR4 N-terminus containing no sulfotyrosines

PDB ID 2k04

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