2k01

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{{Seed}}
 
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[[Image:2k01.png|left|200px]]
 
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==Structure of a locked SDF1 dimer==
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The line below this paragraph, containing "STRUCTURE_2k01", creates the "Structure Box" on the page.
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<StructureSection load='2k01' size='340' side='right'caption='[[2k01]]' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[2k01]] is a 2 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=2K01 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K01 FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2k01 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k01 OCA], [https://pdbe.org/2k01 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k01 RCSB], [https://www.ebi.ac.uk/pdbsum/2k01 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k01 ProSAT]</span></td></tr>
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{{STRUCTURE_2k01| PDB=2k01 | SCENE= }}
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</table>
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== Function ==
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[https://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>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k0/2k01_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</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/main_output.php?pdb_ID=2k01 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Stem cell homing and breast cancer metastasis are orchestrated by the chemokine stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4. Here, we report the nuclear magnetic resonance structure of a constitutively dimeric SDF-1 in complex with a CXCR4 fragment that contains three sulfotyrosine residues important for a high-affinity ligand-receptor interaction. CXCR4 bridged the SDF-1 dimer interface so that sulfotyrosines sTyr7 and sTyr12 of CXCR4 occupied positively charged clefts on opposing chemokine subunits. Dimeric SDF-1 induced intracellular Ca2+ mobilization but had no chemotactic activity; instead, it prevented native SDF-1-induced chemotaxis, suggesting that it acted as a potent partial agonist. Our work elucidates the structural basis for sulfotyrosine recognition in the chemokine-receptor interaction and suggests a strategy for CXCR4-targeted drug development.
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===Structure of a locked SDF1 dimer===
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Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12.,Veldkamp CT, Seibert C, Peterson FC, De la Cruz NB, Haugner JC 3rd, Basnet H, Sakmar TP, Volkman BF Sci Signal. 2008 Sep 16;1(37):ra4. PMID:18799424<ref>PMID:18799424</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2k01" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_18799424}}, adds the Publication Abstract to the page
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*[[C-X-C motif chemokine 3D structures|C-X-C motif chemokine 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 18799424 is the PubMed ID number.
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*[[Stromal Derived Factor 1|Stromal Derived Factor 1]]
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== References ==
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{{ABSTRACT_PUBMED_18799424}}
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<references/>
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__TOC__
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==About this Structure==
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</StructureSection>
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2K01 is a 2 chains structure of sequences 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=2K01 OCA].
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==Reference==
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<ref group="xtra">PMID:18799424</ref><references group="xtra"/>
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[[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: Alternative splicing]]
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[[Category: Volkman BF]]
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[[Category: Chemokine]]
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[[Category: Chemotaxis]]
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[[Category: Cxcl12]]
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[[Category: Cytokine]]
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[[Category: Growth factor]]
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[[Category: Locked dimer]]
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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: Sulfotyrosine]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 10:27:29 2009''
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Current revision

Structure of a locked SDF1 dimer

PDB ID 2k01

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