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| | ==Crystal structure of tablysin-15== | | ==Crystal structure of tablysin-15== |
| - | <StructureSection load='3u3n' size='340' side='right' caption='[[3u3n]], [[Resolution|resolution]] 1.65Å' scene=''> | + | <StructureSection load='3u3n' size='340' side='right'caption='[[3u3n]], [[Resolution|resolution]] 1.65Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3u3n]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Horsefly Horsefly]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U3N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U3N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3u3n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Tabanus_yao Tabanus yao]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U3N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U3N FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=PR:PRASEODYMIUM+ION'>PR</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]] 1.651Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3u3u|3u3u]], [[3u31|3u31]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=PLM:PALMITIC+ACID'>PLM</scene>, <scene name='pdbligand=PR:PRASEODYMIUM+ION'>PR</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=3u3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u3n OCA], [http://pdbe.org/3u3n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u3n RCSB], [http://www.ebi.ac.uk/pdbsum/3u3n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u3n 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=3u3n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u3n OCA], [https://pdbe.org/3u3n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u3n RCSB], [https://www.ebi.ac.uk/pdbsum/3u3n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u3n ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/LYSF_TABYA LYSF_TABYA] Anti-inflammatory scavenger of eicosanoids and antithrombotic protein that inhibits platelets aggregation induced by collagen, ADP and convulxin (GPVI agonist) (PubMed:21475772, PubMed:22311975). Exhibits high affinity binding for glycoprotein IIb-IIIa receptor (ITGA2B/ITGB3) and endothelial cell alphaVbeta3 (ITGAV/ITGB3) integrins, but not for alpha-5/beta-1 or alpha-2/beta-1 (PubMed:21475772). Accordingly, it blocks endothelial cell adhesion to vitronectin (IC(50)~1 nM) and marginally to fibronectin (IC(50)~1 uM), but not to collagen (PubMed:21475772). It also inhibits fibroblast growth factor (FGF)-induced endothelial cell proliferation, and attenuates tube formation in vitro (PubMed:21475772). In addition, it dose-dependently attenuates thrombus formation to collagen under flow (PubMed:21475772). Also binds proinflammatory cysteinyl leukotrienes (leukotrienes C4 (LTC4), D4 (LTD4) and E4 (LTE4)) with submicromolar affinities (PubMed:22311975).<ref>PMID:21475772</ref> <ref>PMID:22311975</ref> |
| | <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: Horsefly]] | + | [[Category: Large Structures]] |
| - | [[Category: Andersen, J F]] | + | [[Category: Tabanus yao]] |
| - | [[Category: Alphavbeta3 integrin]] | + | [[Category: Andersen JF]] |
| - | [[Category: Binding protein]]
| + | |
| - | [[Category: Cap domain]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| - | [[Category: Salivary gland]]
| + | |
| Structural highlights
Function
LYSF_TABYA Anti-inflammatory scavenger of eicosanoids and antithrombotic protein that inhibits platelets aggregation induced by collagen, ADP and convulxin (GPVI agonist) (PubMed:21475772, PubMed:22311975). Exhibits high affinity binding for glycoprotein IIb-IIIa receptor (ITGA2B/ITGB3) and endothelial cell alphaVbeta3 (ITGAV/ITGB3) integrins, but not for alpha-5/beta-1 or alpha-2/beta-1 (PubMed:21475772). Accordingly, it blocks endothelial cell adhesion to vitronectin (IC(50)~1 nM) and marginally to fibronectin (IC(50)~1 uM), but not to collagen (PubMed:21475772). It also inhibits fibroblast growth factor (FGF)-induced endothelial cell proliferation, and attenuates tube formation in vitro (PubMed:21475772). In addition, it dose-dependently attenuates thrombus formation to collagen under flow (PubMed:21475772). Also binds proinflammatory cysteinyl leukotrienes (leukotrienes C4 (LTC4), D4 (LTD4) and E4 (LTE4)) with submicromolar affinities (PubMed:22311975).[1] [2]
Publication Abstract from PubMed
The antihemostatic/antiangiogenic protein tablysin-15 is a member of the cysteine-rich secretory, antigen 5 and pathogenesis-related 1 protein (CAP) superfamily and has been shown to bind the integrins alphaIIbbeta3 and alphaVbeta3 by means of an Arg-Gly-Asp (RGD) tripeptide sequence. Here we describe the X-ray crystal structure of tablysin-15 and show that the RGD motif is located in a novel structural context. The motif itself is contained in a type II beta-turn structure that is similar in its conformation to the RGD sequence of the cyclic pentapeptide cilengitide when bound to integrin alphaVbeta3. The CAP domain also contains a hydrophobic channel that appears to bind a fatty acid molecule in the crystal structure after purification from Escherichia coli. After delipidation of the protein, tablysin-15 was found to bind proinflammatory cysteinyl leukotrienes with submicromolar affinities. The structure of the leukotriene E4 (LTE4)-tablysin-15 complex shows that the ligand binds with the non-functionalized end of the fatty acid chain buried in the hydrophobic pocket, while the carboxylate end of the ligand binds forms hydrogen bond/salt bridge interactions with polar side chains at the channel entrance. Therefore, tablysin-15 functions as an inhibitor of integrin function and as an anti-inflammatory scavenger of eicosanoids.
Structure of a protein having inhibitory disintegrin and leukotriene scavenging functions contained in a single domain.,Xu X, Francischetti IM, Lai R, Ribeiro JM, Andersen JF J Biol Chem. 2012 Feb 6. PMID:22311975[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ma D, Xu X, An S, Liu H, Yang X, Andersen JF, Wang Y, Tokumasu F, Ribeiro JM, Francischetti IM, Lai R. A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets αIIbβ3 or αVβ3 and inhibits platelet aggregation and angiogenesis. Thromb Haemost. 2011 Jun;105(6):1032-45. PMID:21475772 doi:10.1160/TH11-01-0029
- ↑ Xu X, Francischetti IM, Lai R, Ribeiro JM, Andersen JF. Structure of a protein having inhibitory disintegrin and leukotriene scavenging functions contained in a single domain. J Biol Chem. 2012 Feb 6. PMID:22311975 doi:10.1074/jbc.M112.340471
- ↑ Xu X, Francischetti IM, Lai R, Ribeiro JM, Andersen JF. Structure of a protein having inhibitory disintegrin and leukotriene scavenging functions contained in a single domain. J Biol Chem. 2012 Feb 6. PMID:22311975 doi:10.1074/jbc.M112.340471
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