View source for 4zm8


==Crystal Structure of Sialostatin L==
<StructureSection load='4zm8' size='340' side='right'caption='[[4zm8]], [[Resolution|resolution]] 2.68&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zm8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Ixodes_scapularis Ixodes scapularis]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3li7 3li7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZM8 FirstGlance]. <br>
</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=4zm8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zm8 OCA], [https://pdbe.org/4zm8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zm8 RCSB], [https://www.ebi.ac.uk/pdbsum/4zm8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zm8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CYTL_IXOSC CYTL_IXOSC] Inhibitor of cysteine proteinases. Inhibits host immune responses via its inhibition of host cathepsins (PubMed:19494265). Contributes to the suppression of the host's immune response to tick salivary proteins and is important for successful feeding on hosts (PubMed:17698852). Inhibits differentiation of host dendritic cells (PubMed:19494265, PubMed:25975355). Inhibits proliferation of host T-cells in response to antigen stimulus (PubMed:19494265). Down-regulates TLR2-mediated host responses to infection by B.burgdorferi and the production of the chemokine CCL3 by host dendritic cells (PubMed:25975355). Down-regulates host responses to infection by B.burgdorferi and the production of IFNB1 by host dendritic cells (PubMed:25975355). Down-regulates IL1B production by host mast cells, and this then leads to impaired activation of IL1R1, resulting in decreased IL9 production (PubMed:26078269). Inhibits host inflammatory reactions and recruitment of host neutrophils (PubMed:16772304). Inhibits papain and cathepsin-L (CTSL) (in vitro) (PubMed:16772304, PubMed:17698852, PubMed:20545851). Inhibits cathepsin-S (CTSS) (in vitro) (PubMed:17698852, PubMed:20545851). Inhibits CTSV and CTSC, but to a lesser degree (in vitro) (PubMed:16772304, PubMed:17698852).<ref>PMID:16772304</ref> <ref>PMID:17698852</ref> <ref>PMID:19494265</ref> <ref>PMID:20545851</ref> <ref>PMID:25975355</ref> <ref>PMID:26078269</ref> 
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== 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<ref>PMID:20545851</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4zm8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Ixodes scapularis]]
[[Category: Large Structures]]
[[Category: Andersen JF]]
[[Category: Kosyfakis M]]