5d3d

From Proteopedia

(Difference between revisions)

Revision as of 10:19, 21 June 2023

Crystal structure of Staphylococcal Superantigen-Like protein 3

Structural highlights

5d3d is a 2 chain structure with sequence from Staphylococcus aureus subsp. aureus NCTC 8325. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SSL3_STAA8 Secreted protein that plays an essential role in immune innate response inhibition by interacting with and inhibiting host TLR2. In turn, bacteria recognition by immune cells is impaired and cytokine production is inhibited (PubMed:22665377, PubMed:22714643). Mechanistically, by interacting with TLR2, blocks ligand binding and thus inhibits activation (PubMed:26283364). Second, by interacting with an already formed TLR2-lipopeptide complex, prevents TLR heterodimerization and downstream signaling. The interaction with host TLR2 does not involve sialyl Lewis X interactions (PubMed:26283364).^[1] ^[2] ^[3]

Publication Abstract from PubMed

Toll-like receptors (TLRs) are crucial in innate recognition of invading micro-organisms and their subsequent clearance. Bacteria are not passive bystanders and have evolved complex evasion mechanisms. Staphylococcus aureus secretes a potent TLR2 antagonist, staphylococcal superantigen-like protein 3 (SSL3), which prevents receptor stimulation by pathogen-associated lipopeptides. Here, we present crystal structures of SSL3 and its complex with TLR2. The structure reveals that formation of the specific inhibitory complex is predominantly mediated by hydrophobic contacts between SSL3 and TLR2 and does not involve interaction of TLR2-glycans with the conserved LewisX binding site of SSL3. In the complex, SSL3 partially covers the entrance to the lipopeptide binding pocket in TLR2, reducing its size by approximately 50%. We show that this is sufficient to inhibit binding of agonist Pam2CSK4 effectively, yet allows SSL3 to bind to an already formed TLR2-Pam2CSK4 complex. The binding site of SSL3 overlaps those of TLR2 dimerization partners TLR1 and TLR6 extensively. Combined, our data reveal a robust dual mechanism in which SSL3 interferes with TLR2 activation at two stages: by binding to TLR2, it blocks ligand binding and thus inhibits activation. Second, by interacting with an already formed TLR2-lipopeptide complex, it prevents TLR heterodimerization and downstream signaling.

Structural basis for inhibition of TLR2 by staphylococcal superantigen-like protein 3 (SSL3).,Koymans KJ, Feitsma LJ, Brondijk TH, Aerts PC, Lukkien E, Lossl P, van Kessel KP, de Haas CJ, van Strijp JA, Huizinga EG Proc Natl Acad Sci U S A. 2015 Aug 17. pii: 201502026. PMID:26283364^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yokoyama R, Itoh S, Kamoshida G, Takii T, Fujii S, Tsuji T, Onozaki K. Staphylococcal superantigen-like protein 3 binds to the Toll-like receptor 2 extracellular domain and inhibits cytokine production induced by Staphylococcus aureus, cell wall component, or lipopeptides in murine macrophages. Infect Immun. 2012 Aug;80(8):2816-25. PMID:22665377 doi:10.1128/IAI.00399-12
↑ Bardoel BW, Vos R, Bouman T, Aerts PC, Bestebroer J, Huizinga EG, Brondijk TH, van Strijp JA, de Haas CJ. Evasion of Toll-like receptor 2 activation by staphylococcal superantigen-like protein 3. J Mol Med (Berl). 2012 Oct;90(10):1109-20. PMID:22714643 doi:10.1007/s00109-012-0926-8
↑ Koymans KJ, Feitsma LJ, Brondijk TH, Aerts PC, Lukkien E, Lossl P, van Kessel KP, de Haas CJ, van Strijp JA, Huizinga EG. Structural basis for inhibition of TLR2 by staphylococcal superantigen-like protein 3 (SSL3). Proc Natl Acad Sci U S A. 2015 Aug 17. pii: 201502026. PMID:26283364 doi:http://dx.doi.org/10.1073/pnas.1502026112
↑ Koymans KJ, Feitsma LJ, Brondijk TH, Aerts PC, Lukkien E, Lossl P, van Kessel KP, de Haas CJ, van Strijp JA, Huizinga EG. Structural basis for inhibition of TLR2 by staphylococcal superantigen-like protein 3 (SSL3). Proc Natl Acad Sci U S A. 2015 Aug 17. pii: 201502026. PMID:26283364 doi:http://dx.doi.org/10.1073/pnas.1502026112

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5d3d"

Categories: Large Structures | Staphylococcus aureus subsp. aureus NCTC 8325 | Feitsma LJ | Huizinga EG

@@ Line 3: / Line 3: @@
 <StructureSection load='5d3d' size='340' side='right'caption='[[5d3d]], [[Resolution|resolution]] 1.94&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5d3d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Staa8 Staa8]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D3D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5D3D FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5d3d]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_NCTC_8325 Staphylococcus aureus subsp. aureus NCTC 8325]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5D3D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5D3D FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SAOUHSC_00386 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=93061 STAA8])</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=5d3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d3d OCA], [https://pdbe.org/5d3d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5d3d RCSB], [https://www.ebi.ac.uk/pdbsum/5d3d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5d3d ProSAT]</span></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=5d3d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5d3d OCA], [http://pdbe.org/5d3d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5d3d RCSB], [http://www.ebi.ac.uk/pdbsum/5d3d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5d3d ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/SSL3_STAA8 SSL3_STAA8] Secreted protein that plays an essential role in immune innate response inhibition by interacting with and inhibiting host TLR2. In turn, bacteria recognition by immune cells is impaired and cytokine production is inhibited (PubMed:22665377, PubMed:22714643). Mechanistically, by interacting with TLR2, blocks ligand binding and thus inhibits activation (PubMed:26283364). Second, by interacting with an already formed TLR2-lipopeptide complex, prevents TLR heterodimerization and downstream signaling. The interaction with host TLR2 does not involve sialyl Lewis X interactions (PubMed:26283364).<ref>PMID:22665377</ref> <ref>PMID:22714643</ref> <ref>PMID:26283364</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Staa8]]
+[[Category: Staphylococcus aureus subsp. aureus NCTC 8325]]
-[[Category: Feitsma, L J]]
+[[Category: Feitsma LJ]]
-[[Category: Huizinga, E G]]
+[[Category: Huizinga EG]]
-[[Category: Immune system]]
-[[Category: Immunology]]
-[[Category: Inflammation]]
-[[Category: Inhibition]]
-[[Category: Ssl]]
-[[Category: Ssl3]]
-[[Category: Superantigen]]
-[[Category: Superantigen-like protein]]
-[[Category: Tlr2]]
-[[Category: Toll-like receptor 2]]

5d3d

From Proteopedia

Revision as of 10:19, 21 June 2023

Crystal structure of Staphylococcal Superantigen-Like protein 3

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox