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6stk

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Crystal structure of the CC-chemokine 5 (CCL5) E66S mutation

Structural highlights

6stk 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 1.52Å
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]

Publication Abstract from PubMed

Ticks, as blood sucking parasites, have developed a complex strategy to evade and suppress host immune responses during feeding. The crucial part of this strategy is expression of a broad family of salivary proteins, called Evasins, to neutralize chemokines responsible for cell trafficking and recruitment. However, structural information about Evasins is still scarce and little is known about the structural determinants of their binding mechanism to chemokines. Here, we studied the structurally uncharacterized Evasin-4, which neutralizes a broad range of CC-motif chemokines, including the chemokine CC-motif ligand 5 (CCL5) involved in atherogenesis. Crystal structures of Evasin-4 and E66S CCL5-an obligatory dimeric variant of CCL5-were determined to a resolution of 1.3-1.8 A. The Evasin-4 crystal structure revealed an L-shaped architecture formed by an N- and C-terminal subdomain consisting of eight beta-strands and an alpha-helix that adopts a substantially different position compared to closely related Evasin-1. Further investigation into E66S CCL5/Evasin-4 complex formation with NMR spectroscopy showed that residues of the N-terminus are involved in binding to CCL5. The peptide derived from the N-terminal region of Evasin-4 possessed nM affinity to CCL5 and inhibited CCL5 activity in monocyte migration assays. This suggests that Evasin-4 derivatives could be used as starting point for the development of anti-inflammatory drugs.

Structural characterization of anti-CCL5 activity of the tick salivary protein Evasin-4.,Denisov SS, Ramirez-Escudero M, Heinzmann ACA, Ippel JH, Dawson PE, Koenen RR, Hackeng TM, Janssen BJC, Dijkgraaf I J Biol Chem. 2020 Aug 14. pii: RA120.013891. doi: 10.1074/jbc.RA120.013891. PMID:32817341^[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
↑ Denisov SS, Ramirez-Escudero M, Heinzmann ACA, Ippel JH, Dawson PE, Koenen RR, Hackeng TM, Janssen BJC, Dijkgraaf I. Structural characterization of anti-CCL5 activity of the tick salivary protein Evasin-4. J Biol Chem. 2020 Aug 14. pii: RA120.013891. doi: 10.1074/jbc.RA120.013891. PMID:32817341 doi:http://dx.doi.org/10.1074/jbc.RA120.013891

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6stk"

Categories: Homo sapiens | Large Structures | Janssen BJC | Ramirez-Escudero M

@@ Line 3: / Line 3: @@
 <StructureSection load='6stk' size='340' side='right'caption='[[6stk]], [[Resolution|resolution]] 1.52&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6stk]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6STK OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6STK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6stk]] 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=6STK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6STK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.52&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5coy|5coy]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCL5, D17S136E, SCYA5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6stk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6stk OCA], [https://pdbe.org/6stk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6stk RCSB], [https://www.ebi.ac.uk/pdbsum/6stk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6stk ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6stk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6stk OCA], [http://pdbe.org/6stk PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6stk RCSB], [http://www.ebi.ac.uk/pdbsum/6stk PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6stk ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Janssen, B J.C]]
+[[Category: Janssen BJC]]
-[[Category: Ramirez-Escudero, M]]
+[[Category: Ramirez-Escudero M]]
-[[Category: Cc-chemokine]]
-[[Category: Immune system]]

6stk

From Proteopedia

Current revision

Crystal structure of the CC-chemokine 5 (CCL5) E66S mutation

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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