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1u4m

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human RANTES complexed to heparin-derived disaccharide III-S

Structural highlights

1u4m is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4] ^[5]

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 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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Capoulade-Metay C, Ayouba A, Kfutwah A, Lole K, Petres S, Dudoit Y, Deterre P, Menu E, Barre-Sinoussi F, Debre P, Theodorou I. A natural CCL5/RANTES variant antagonist for CCR1 and CCR3. Immunogenetics. 2006 Jul;58(7):533-41. Epub 2006 Jun 22. PMID:16791620 doi:http://dx.doi.org/10.1007/s00251-006-0133-2
↑ Kameyoshi Y, Dorschner A, Mallet AI, Christophers E, Schroder JM. Cytokine RANTES released by thrombin-stimulated platelets is a potent attractant for human eosinophils. J Exp Med. 1992 Aug 1;176(2):587-92. PMID:1380064
↑ Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15;270(5243):1811-5. PMID:8525373
↑ Proost P, De Meester I, Schols D, Struyf S, Lambeir AM, Wuyts A, Opdenakker G, De Clercq E, Scharpe S, Van Damme J. Amino-terminal truncation of chemokines by CD26/dipeptidyl-peptidase IV. Conversion of RANTES into a potent inhibitor of monocyte chemotaxis and HIV-1-infection. J Biol Chem. 1998 Mar 27;273(13):7222-7. PMID:9516414
↑ Lim JK, Burns JM, Lu W, DeVico AL. Multiple pathways of amino terminal processing produce two truncated variants of RANTES/CCL5. J Leukoc Biol. 2005 Aug;78(2):442-52. Epub 2005 May 27. PMID:15923218 doi:http://dx.doi.org/jlb.0305161
↑ Shaw JP, Johnson Z, Borlat F, Zwahlen C, Kungl A, Roulin K, Harrenga A, Wells TN, Proudfoot AE. The X-ray structure of RANTES: heparin-derived disaccharides allows the rational design of chemokine inhibitors. Structure. 2004 Nov;12(11):2081-93. PMID:15530372 doi:10.1016/j.str.2004.08.014

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1u4m"

@@ Line 1: / Line 1: @@
 ==human RANTES complexed to heparin-derived disaccharide III-S==
-<StructureSection load='1u4m' size='340' side='right' caption='[[1u4m]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='1u4m' size='340' side='right'caption='[[1u4m]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1u4m]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1U4M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1U4M FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1u4m]] 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=1U4M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1U4M FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=H3S:HEPARIN+DISACCHARIDE+III-S'>H3S</scene><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]] 2&#8491;</td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1hrj|1hrj]], [[1rtn|1rtn]], [[1rto|1rto]], [[1b3a|1b3a]], [[1eqt|1eqt]], [[1u4r|1u4r]], [[1u4l|1u4l]], [[1u4p|1u4p]]</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=GNS:N-SULFO-ALPHA-D-GLUCOSAMINE'>GNS</scene>, <scene name='pdbligand=PRD_900094:HEPARIN+DISACCHARIDE+III-S'>PRD_900094</scene>, <scene name='pdbligand=UAP:4-DEOXY-2-O-SULFO-ALPHA-L-THREO-HEX-4-ENOPYRANURONIC+ACID'>UAP</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL5, SCYA5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</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=1u4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u4m OCA], [https://pdbe.org/1u4m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1u4m RCSB], [https://www.ebi.ac.uk/pdbsum/1u4m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1u4m ProSAT]</span></td></tr>
-<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=1u4m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1u4m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1u4m RCSB], [http://www.ebi.ac.uk/pdbsum/1u4m PDBsum]</span></td></tr>
+</table>
-<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/u4/1u4m_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/u4/1u4m_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=1u4m ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1u4m" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 31: / Line 34: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Borlat, F.]]
+[[Category: Large Structures]]
-[[Category: Harrenga, A.]]
+[[Category: Borlat F]]
-[[Category: Johnson, Z.]]
+[[Category: Harrenga A]]
-[[Category: Kungl, A.]]
+[[Category: Johnson Z]]
-[[Category: Proudfoot, A E.I.]]
+[[Category: Kungl A]]
-[[Category: Roulin, K.]]
+[[Category: Proudfoot AEI]]
-[[Category: Shaw, J P.]]
+[[Category: Roulin K]]
-[[Category: Wells, T N.C.]]
+[[Category: Shaw JP]]
-[[Category: Zwahlen, C.]]
+[[Category: Wells TNC]]
-[[Category: Attractant]]
+[[Category: Zwahlen C]]
-[[Category: Chemoattractant]]
-[[Category: Chemokine]]
-[[Category: Cytokine]]
-[[Category: Glycosaminoglycan]]
-[[Category: Protein-heparin disaccharide complex]]
-[[Category: Rante]]

1u4m

From Proteopedia

Current revision

human RANTES complexed to heparin-derived disaccharide III-S

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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