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| | ==Truncated Evasin-3 (tEv3 17-56)== | | ==Truncated Evasin-3 (tEv3 17-56)== |
| - | <StructureSection load='6qjb' size='340' side='right'caption='[[6qjb]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6qjb' size='340' side='right'caption='[[6qjb]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6qjb]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QJB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6QJB FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6qjb]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhipicephalus_sanguineus Rhipicephalus sanguineus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6QJB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6QJB FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6qjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qjb OCA], [http://pdbe.org/6qjb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6qjb RCSB], [http://www.ebi.ac.uk/pdbsum/6qjb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6qjb ProSAT]</span></td></tr> | + | </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=6qjb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6qjb OCA], [https://pdbe.org/6qjb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6qjb RCSB], [https://www.ebi.ac.uk/pdbsum/6qjb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6qjb ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/EVA3_RHISA EVA3_RHISA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Denisov, S S]] | + | [[Category: Rhipicephalus sanguineus]] |
| - | [[Category: Dijkgraaf, I]] | + | [[Category: Denisov SS]] |
| - | [[Category: Hackeng, T M]] | + | [[Category: Dijkgraaf I]] |
| - | [[Category: Heinzman, A C.A]] | + | [[Category: Hackeng TM]] |
| - | [[Category: Ippel, J H]] | + | [[Category: Heinzman ACA]] |
| - | [[Category: Koenen, R R]] | + | [[Category: Ippel JH]] |
| - | [[Category: Ortega-Gomez, A]] | + | [[Category: Koenen RR]] |
| - | [[Category: Soehnlein, O]] | + | [[Category: Ortega-Gomez A]] |
| - | [[Category: Chemokine-binding protein]]
| + | [[Category: Soehnlein O]] |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Tick]]
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| Structural highlights
Function
EVA3_RHISA
Publication Abstract from PubMed
Chemokines are a group of chemotaxis proteins that regulate cell trafficking and play important roles in immune responses and inflammation. Ticks are blood-sucking parasites that secrete numerous immune-modulatory agents in their saliva to evade host immune responses. Evasin-3 is a small salivary protein which belongs to a class of chemokine-binding proteins isolated from the brown dog tick, Rhipicephalus sanguineus. Evasin-3 has been shown to have a high affinity for chemokines CXCL1 and CXCL8 and diminish inflammation in mice. In the present study, solution NMR spectroscopy was used to investigate the structure of Evasin-3 and its CXCL8/Evasin-3 complex. Evasin-3 is found to disrupt the glycosaminoglycan (GAG) binding site of CXCL8 and inhibit the interaction of CXCL8 with CXCR2. Structural data were used to design two novel CXCL8 binding peptides. Linear tEv3 17-56 and cyclic tcEv3 16-56 dPG Evasin-3 variants were chemically synthesized by solid phase peptide synthesis. Affinity of these newly synthesized variants to CXCL8 were measured by surface plasmon resonance (SPR) biosensor analysis. Kd values of tEv3 17-56 and tcEv3 16-56 dPG were 27 and 13 nM, respectively. Both compounds effectively inhibited CXCL8 induced migration of polymorphonuclear neutrophils (PMN). The present results suggest utility of synthetic Evasin-3 variants as scaffolds for designing and fine-tuning new chemokine-binding agents that suppress immune responses and inflammation.
Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8 interactions with glycosaminoglycans and CXCR2.,Denisov SS, Ippel JH, Heinzmann ACA, Koenen RR, Ortega-Gomez A, Soehnlein O, Hackeng TM, Dijkgraaf I J Biol Chem. 2019 Jun 24. pii: RA119.008902. doi: 10.1074/jbc.RA119.008902. PMID:31235521[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Denisov SS, Ippel JH, Heinzmann ACA, Koenen RR, Ortega-Gomez A, Soehnlein O, Hackeng TM, Dijkgraaf I. Tick saliva protein Evasin-3 modulates chemotaxis by disrupting CXCL8 interactions with glycosaminoglycans and CXCR2. J Biol Chem. 2019 Jun 24. pii: RA119.008902. doi: 10.1074/jbc.RA119.008902. PMID:31235521 doi:http://dx.doi.org/10.1074/jbc.RA119.008902
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