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6i31
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6i31 is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the tick chemokine-binding protein Evasin-3== | |
| + | <StructureSection load='6i31' size='340' side='right'caption='[[6i31]], [[Resolution|resolution]] 1.79Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6i31]] is a 2 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=6I31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6I31 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene></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=6i31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6i31 OCA], [http://pdbe.org/6i31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6i31 RCSB], [http://www.ebi.ac.uk/pdbsum/6i31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6i31 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tick evasins (EVAs) bind either CC or CXC-chemokines by a poorly understood promiscuous or "one-to-many" mechanism to neutralize inflammation. Since EVAs potently inhibit inflammation in many pre-clinical models, highlighting their potential as biological therapeutics for inflammatory diseases, we sought to further unravel the CXC-chemokine-EVA interactions. Using yeast surface display, we identified and characterized 27 novel CXC-chemokine-binding evasins homologous to EVA3 and defined two functional classes. The first, which included EVA3, exclusively bound ELR+ CXC-chemokines, whereas the second class bound both ELR+ and ELR- CXC-chemokines, in several cases including C-X-C motif chemokine ligand 10 (CXCL10), but, surprisingly, not CXCL8. The X-ray crystal structure of EVA3 at a resolution of 1.79 A revealed a single anti-parallel b-sheet with six conserved cysteine residues forming a disulfide-bonded knottin scaffold which creates a contiguous solvent-accessible surface. Swapping analyses identified distinct knottin scaffold segments necessary for different CXC-chemokine-binding activities, implying that differential ligand positioning, at least in part, plays a role in promiscuous binding. Swapping segments also transferred chemokine-binding activity, resulting in a hybrid EVA with dual CXCL10- and CXCL8-binding activities. The solvent-accessible surfaces of the knottin scaffold segments have distinctive shape and charge, which we suggest drives chemokine binding specificity. These studies provide structural and mechanistic insight into how CXC-chemokine-binding tick EVAs achieve class specificity but also engage in promiscuous binding. | ||
| - | + | A knottin scaffold directs the CXC-chemokine-binding specificity of tick evasins.,Lee AW, Deruaz M, Lynch C, Davies G, Singh K, Alenazi Y, Eaton JRO, Kawamura A, Shaw J, Proudfoot AEI, Dias JM, Bhattacharya S J Biol Chem. 2019 Jun 5. pii: RA119.008817. doi: 10.1074/jbc.RA119.008817. PMID:31167786<ref>PMID:31167786</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6i31" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Brown dog tick]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Dias, J M]] | ||
| + | [[Category: Shaw, J P]] | ||
| + | [[Category: Chemokine-binding tick evasin saliva]] | ||
| + | [[Category: Peptide binding protein]] | ||
Current revision
Crystal structure of the tick chemokine-binding protein Evasin-3
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