2k04: Difference between revisions
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==Structure of SDF1 in complex with the CXCR4 N-terminus containing no sulfotyrosines== | |||
<StructureSection load='2k04' size='340' side='right'caption='[[2k04]]' scene=''> | |||
== Structural highlights == | |||
<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> | |||
</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> | |||
<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> | |||
</table> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/k0/2k04_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2k04" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[C-X-C motif chemokine 3D structures|C-X-C motif chemokine 3D structures]] | |||
*[[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]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Peterson FC]] | ||
[[Category: | [[Category: Veldkamp CT]] | ||
[[Category: | [[Category: Volkman BF]] | ||
Latest revision as of 09:09, 27 November 2024
Structure of SDF1 in complex with the CXCR4 N-terminus containing no sulfotyrosinesStructure of SDF1 in complex with the CXCR4 N-terminus containing no sulfotyrosines
Structural highlights
Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedStem 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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also
References |
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