2k03

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{{Seed}}
 
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[[Image:2k03.jpg|left|200px]]
 
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==Structure of SDF1 in complex with the CXCR4 N-terminus containing a sulfotyrosine at postition 21==
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The line below this paragraph, containing "STRUCTURE_2k03", creates the "Structure Box" on the page.
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<StructureSection load='2k03' size='340' side='right'caption='[[2k03]]' scene=''>
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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'>[[2k03]] 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=2K03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K03 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">Solution NMR, 20 models</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=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
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{{STRUCTURE_2k03| PDB=2k03 | SCENE= }}
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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=2k03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k03 OCA], [https://pdbe.org/2k03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k03 RCSB], [https://www.ebi.ac.uk/pdbsum/2k03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k03 ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/CXCR4_HUMAN CXCR4_HUMAN] Defects in CXCR4 are a cause of WHIM syndrome (WHIM) [MIM:[https://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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[https://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 ==
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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/k0/2k03_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=2k03 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 SDF1 in complex with the CXCR4 N-terminus containing a sulfotyrosine at postition 21===
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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 2k03" 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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*[[CXC chemokine receptor|CXC chemokine receptor]]
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*[[CXC chemokine receptor type 4|CXC chemokine receptor type 4]]
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{{ABSTRACT_PUBMED_18799424}}
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*[[Stromal Derived Factor 1|Stromal Derived Factor 1]]
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== References ==
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==Disease==
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<references/>
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Known disease associated with this structure: Myelokathexis, isolated OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=162643 162643]], WHIM syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=162643 162643]]
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__TOC__
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</StructureSection>
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==About this Structure==
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2K03 is a [[Protein complex]] 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=2K03 OCA].
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==Reference==
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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:[http://www.ncbi.nlm.nih.gov/pubmed/18799424 18799424]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Peterson, F C.]]
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[[Category: Peterson FC]]
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[[Category: Veldkamp, C T.]]
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[[Category: Veldkamp CT]]
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[[Category: Volkman, B F.]]
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[[Category: Volkman BF]]
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[[Category: Alternative splicing]]
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[[Category: Chemokine]]
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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: Sulfotyrosine]]
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[[Category: Transducer]]
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[[Category: Transmembrane]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 29 10:44:09 2008''
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Current revision

Structure of SDF1 in complex with the CXCR4 N-terminus containing a sulfotyrosine at postition 21

PDB ID 2k03

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