1u4l
From Proteopedia
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- | {{Seed}} | ||
- | [[Image:1u4l.png|left|200px]] | ||
- | + | ==human RANTES complexed to heparin-derived disaccharide I-S== | |
- | + | <StructureSection load='1u4l' size='340' side='right'caption='[[1u4l]], [[Resolution|resolution]] 2.00Å' scene=''> | |
- | + | == Structural highlights == | |
- | + | <table><tr><td colspan='2'>[[1u4l]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U4L FirstGlance]. <br> | |
- | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | |
- | - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=PRD_900026:HEPARIN+DISACCHARIDE+I-S,'>PRD_900026</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene>, <scene name='pdbligand=UAP:4-DEOXY-2-O-SULFO-ALPHA-L-THREO-HEX-4-ENOPYRANURONIC+ACID'>UAP</scene></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=1u4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u4l OCA], [https://pdbe.org/1u4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u4l RCSB], [https://www.ebi.ac.uk/pdbsum/1u4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u4l ProSAT]</span></td></tr> | |
+ | </table> | ||
+ | == Function == | ||
+ | [https://www.uniprot.org/uniprot/CCL5_HUMAN CCL5_HUMAN] Chemoattractant for blood monocytes, memory T-helper cells and eosinophils. Causes the release of histamine from basophils and activates eosinophils. Binds to CCR1, CCR3, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant RANTES protein induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form RANTES(3-68) acts as a natural chemotaxis inhibitor and is a more potent inhibitor of HIV-1-infection. The second processed form RANTES(4-68) exhibits reduced chemotactic and HIV-suppressive activity compared with RANTES(1-68) and RANTES(3-68) and is generated by an unidentified enzyme associated with monocytes and neutrophils.<ref>PMID:16791620</ref> <ref>PMID:1380064</ref> <ref>PMID:8525373</ref> <ref>PMID:9516414</ref> <ref>PMID:15923218</ref> | ||
+ | == 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/u4/1u4l_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=1u4l ConSurf]. | ||
+ | <div style="clear:both"></div> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | The biological activity of chemokines requires interactions with cell surface proteoglycans. We have determined the structure of the chemokine RANTES (regulated on activation normal T cell expressed) in the presence of heparin-derived disaccharide analogs by X-ray crystallography. These structures confirm the essential role of the BBXB motif in the interaction between the chemokine and the disaccharide. Unexpected interactions were observed in the 30s loop and at the amino terminus. Mutant RANTES molecules were designed to abrogate these interactions and their biological activity examined in vivo. The K45E mutant within the BBXB motif lost the capacity to bind heparin and the ability to elicit cellular recruitment. The Y3A mutant maintained its capacity to bind heparin but was unable to elicit cellular recruitment. Finally, a tetrasaccharide is the smallest oligosaccharide which effectively abolishes the ability of RANTES to recruit cells in vivo. These crystallographic structures provide a description of the molecular interaction of a chemokine with glycosaminoglycans. | ||
- | + | The X-ray structure of RANTES: heparin-derived disaccharides allows the rational design of chemokine inhibitors.,Shaw JP, Johnson Z, Borlat F, Zwahlen C, Kungl A, Roulin K, Harrenga A, Wells TN, Proudfoot AE Structure. 2004 Nov;12(11):2081-93. PMID:15530372<ref>PMID:15530372</ref> | |
- | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
- | + | </div> | |
- | + | <div class="pdbe-citations 1u4l" style="background-color:#fffaf0;"></div> | |
- | + | == References == | |
- | + | <references/> | |
- | + | __TOC__ | |
- | + | </StructureSection> | |
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
- | [[Category: Borlat | + | [[Category: Large Structures]] |
- | [[Category: Harrenga | + | [[Category: Borlat F]] |
- | [[Category: Johnson | + | [[Category: Harrenga A]] |
- | [[Category: Kungl | + | [[Category: Johnson Z]] |
- | [[Category: Proudfoot | + | [[Category: Kungl A]] |
- | [[Category: Roulin | + | [[Category: Proudfoot AEI]] |
- | [[Category: Shaw | + | [[Category: Roulin K]] |
- | [[Category: Wells | + | [[Category: Shaw JP]] |
- | [[Category: Zwahlen | + | [[Category: Wells TNC]] |
- | + | [[Category: Zwahlen C]] | |
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Current revision
human RANTES complexed to heparin-derived disaccharide I-S
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Categories: Homo sapiens | Large Structures | Borlat F | Harrenga A | Johnson Z | Kungl A | Proudfoot AEI | Roulin K | Shaw JP | Wells TNC | Zwahlen C