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| | <StructureSection load='6stc' size='340' side='right'caption='[[6stc]], [[Resolution|resolution]] 1.69Å' scene=''> | | <StructureSection load='6stc' size='340' side='right'caption='[[6stc]], [[Resolution|resolution]] 1.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6stc]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Brown_dog_tick Brown dog tick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6STC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6STC FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6stc]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhipicephalus_sanguineus Rhipicephalus sanguineus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6STC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6STC 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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</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]] 1.69Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6st4|6st4]]</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=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene></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=6stc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6stc OCA], [http://pdbe.org/6stc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6stc RCSB], [http://www.ebi.ac.uk/pdbsum/6stc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6stc ProSAT]</span></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=6stc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6stc OCA], [https://pdbe.org/6stc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6stc RCSB], [https://www.ebi.ac.uk/pdbsum/6stc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6stc ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/EVA4_RHISA EVA4_RHISA] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Brown dog tick]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Janssen, B J.C]] | + | [[Category: Rhipicephalus sanguineus]] |
| - | [[Category: Ramirez-Escudero, M]] | + | [[Category: Janssen BJC]] |
| - | [[Category: Chemokine-binding protein]] | + | [[Category: Ramirez-Escudero M]] |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Tick]]
| + | |
| Structural highlights
Function
EVA4_RHISA
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
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