3lh4

From Proteopedia

(Difference between revisions)

Current revision

Crystal Structure of Sialostatin L2

Structural highlights

3lh4 is a 1 chain structure with sequence from Ixodes scapularis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3lh4"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Sialostatin L2==
-<StructureSection load='3lh4' size='340' side='right' caption='[[3lh4]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+<StructureSection load='3lh4' size='340' side='right'caption='[[3lh4]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3lh4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Ixodes_scapularis Ixodes scapularis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3LH4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3LH4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3lh4]] 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=3LH4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3LH4 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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]] 1.8&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IscW_ISCW018602 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=6945 Ixodes scapularis])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3lh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lh4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3lh4 RCSB], [http://www.ebi.ac.uk/pdbsum/3lh4 PDBsum]</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=3lh4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3lh4 OCA], [https://pdbe.org/3lh4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3lh4 RCSB], [https://www.ebi.ac.uk/pdbsum/3lh4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3lh4 ProSAT]</span></td></tr>
 </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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lh/3lh4_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lh/3lh4_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>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3lh4 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 25: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3lh4" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 30: / Line 34: @@
 </StructureSection>
 [[Category: Ixodes scapularis]]
-[[Category: Andersen, J F]]
+[[Category: Large Structures]]
-[[Category: Horka, H]]
+[[Category: Andersen JF]]
-[[Category: Kotsyfakis, M]]
+[[Category: Horka H]]
-[[Category: Salat, J]]
+[[Category: Kotsyfakis M]]
-[[Category: Beta sheet]]
+[[Category: Salat J]]
-[[Category: Cystatin]]
-[[Category: Hydrolase inhibitor]]
-[[Category: Protease inhibitor]]
-[[Category: Thiol protease inhibitor]]

3lh4

From Proteopedia

Current revision

Crystal Structure of Sialostatin L2

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox