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| | <StructureSection load='3mwz' size='340' side='right'caption='[[3mwz]], [[Resolution|resolution]] 1.52Å' scene=''> | | <StructureSection load='3mwz' size='340' side='right'caption='[[3mwz]], [[Resolution|resolution]] 1.52Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3mwz]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Black-legged_tick Black-legged tick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MWZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=3MWZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3mwz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ixodes_scapularis Ixodes scapularis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3MWZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3MWZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.52Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3mwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mwz OCA], [http://pdbe.org/3mwz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3mwz RCSB], [http://www.ebi.ac.uk/pdbsum/3mwz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3mwz 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=3mwz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3mwz OCA], [https://pdbe.org/3mwz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3mwz RCSB], [https://www.ebi.ac.uk/pdbsum/3mwz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3mwz ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CYTL2_IXOSC CYTL2_IXOSC] Inhibitor of cysteine proteinases. Inhibits host immune responses, probably via its inhibition of host cathepsins. Contributes to the suppression of the host's immune response to tick salivary proteins and is important for successful feeding on hosts (PubMed:17698852). Down-regulates TLR2-mediated host responses to infection by B.burgdorferi and the production of chemokines CCL3 and CXCL10 by host dendritic cells (PubMed:25975355). Enhances infection by the tick-transmitted pathogen B.burgdorferi (in vitro) (PubMed:20545851). Inhibits host inflammatory responses to A.phagocytophilum infection (PubMed:24686067). Inhibits papain (in vitro) (PubMed:20545851). Inhibits cathepsin-L (CTSL) (in vitro) (PubMed:17698852, PubMed:20545851). Inhibits cathepsin-L2 (CTSV) (in vitro) (PubMed:17698852).<ref>PMID:17698852</ref> <ref>PMID:20545851</ref> <ref>PMID:24686067</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mw/3mwz_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/mw/3mwz_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Black-legged tick]] | + | [[Category: Ixodes scapularis]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Andersen, J F]] | + | [[Category: Andersen JF]] |
| - | [[Category: Antiparallel beta-sheet]]
| + | |
| - | [[Category: Hydrolase inhibitor]]
| + | |
| Structural highlights
Function
CYTL2_IXOSC Inhibitor of cysteine proteinases. Inhibits host immune responses, probably via its inhibition of host cathepsins. Contributes to the suppression of the host's immune response to tick salivary proteins and is important for successful feeding on hosts (PubMed:17698852). Down-regulates TLR2-mediated host responses to infection by B.burgdorferi and the production of chemokines CCL3 and CXCL10 by host dendritic cells (PubMed:25975355). Enhances infection by the tick-transmitted pathogen B.burgdorferi (in vitro) (PubMed:20545851). Inhibits host inflammatory responses to A.phagocytophilum infection (PubMed:24686067). Inhibits papain (in vitro) (PubMed:20545851). Inhibits cathepsin-L (CTSL) (in vitro) (PubMed:17698852, PubMed:20545851). Inhibits cathepsin-L2 (CTSV) (in vitro) (PubMed:17698852).[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We have previously demonstrated that two salivary cysteine protease inhibitors from the Borrelia burgdorferi (Lyme disease) vector Ixodes scapularis- namely sialostatins L and L2 - play an important role in tick biology, as demonstrated by the fact that silencing of both sialostatins in tandem results in severe feeding defects. Here we show that sialostatin L2 - but not sialostatin L - facilitates the growth of B. burgdorferi in murine skin. To examine the structural basis underlying these differential effects of the two sialostatins, we have determined the crystal structures of both sialostatin L and L2. This is the first structural analysis of cystatins from an invertebrate source. Sialostatin L2 crystallizes as a monomer with an 'unusual' conformation of the N-terminus, while sialostatin L crystallizes as a domain-swapped dimer with an N-terminal conformation similar to other cystatins. Deletion of the 'unusual' N-terminal five residues of sialostatin L2 results in marked changes in its selectivity, suggesting that this region is a particularly important determinant of the biochemical activity of sialostatin L2. Collectively, our results reveal the structure of two tick salivary components that facilitate vector blood feeding and that one of them also supports pathogen transmission to the vertebrate host.
The crystal structures of two salivary cystatins from the tick Ixodes scapularis and the effect of these inhibitors on the establishment of Borrelia burgdorferi infection in a murine model.,Kotsyfakis M, Horka H, Salat J, Andersen JF Mol Microbiol. 2010 Jul;77(2):456-70. Epub 2010 Jun 1. PMID:20545851[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kotsyfakis M, Karim S, Andersen JF, Mather TN, Ribeiro JM. Selective cysteine protease inhibition contributes to blood-feeding success of the tick Ixodes scapularis. J Biol Chem. 2007 Oct 5;282(40):29256-63. PMID:17698852 doi:10.1074/jbc.M703143200
- ↑ Kotsyfakis M, Horka H, Salat J, Andersen JF. The crystal structures of two salivary cystatins from the tick Ixodes scapularis and the effect of these inhibitors on the establishment of Borrelia burgdorferi infection in a murine model. Mol Microbiol. 2010 Jul;77(2):456-70. Epub 2010 Jun 1. PMID:20545851 doi:10.1111/j.1365-2958.2010.07220.x
- ↑ Chen G, Wang X, Severo MS, Sakhon OS, Sohail M, Brown LJ, Sircar M, Snyder GA, Sundberg EJ, Ulland TK, Olivier AK, Andersen JF, Zhou Y, Shi GP, Sutterwala FS, Kotsyfakis M, Pedra JH. The tick salivary protein sialostatin L2 inhibits caspase-1-mediated inflammation during Anaplasma phagocytophilum infection. Infect Immun. 2014 Jun;82(6):2553-64. PMID:24686067 doi:10.1128/IAI.01679-14
- ↑ Kotsyfakis M, Horka H, Salat J, Andersen JF. The crystal structures of two salivary cystatins from the tick Ixodes scapularis and the effect of these inhibitors on the establishment of Borrelia burgdorferi infection in a murine model. Mol Microbiol. 2010 Jul;77(2):456-70. Epub 2010 Jun 1. PMID:20545851 doi:10.1111/j.1365-2958.2010.07220.x
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