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| | ==Crystal Structure of truncated form of Staphylococcal Complement Inhibitor D (SCIN-D) at 1.3 Angstrom== | | ==Crystal Structure of truncated form of Staphylococcal Complement Inhibitor D (SCIN-D) at 1.3 Angstrom== |
| - | <StructureSection load='3t47' size='340' side='right' caption='[[3t47]], [[Resolution|resolution]] 1.30Å' scene=''> | + | <StructureSection load='3t47' size='340' side='right'caption='[[3t47]], [[Resolution|resolution]] 1.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3t47]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Staam Staam]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T47 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T47 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3t47]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus_subsp._aureus_Mu50 Staphylococcus aureus subsp. aureus Mu50]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T47 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T47 FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3t46|3t46]], [[3t48|3t48]], [[3t49|3t49]], [[3t4a|3t4a]]</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]] 1.301Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SAV0229 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158878 STAAM])</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=3t47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t47 OCA], [https://pdbe.org/3t47 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t47 RCSB], [https://www.ebi.ac.uk/pdbsum/3t47 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t47 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=3t47 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t47 OCA], [http://pdbe.org/3t47 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t47 RCSB], [http://www.ebi.ac.uk/pdbsum/3t47 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t47 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/A0A0H3JPM4_STAAM A0A0H3JPM4_STAAM] Involved in countering the first line of host defense mechanisms. Efficiently inhibits opsonization, phagocytosis and killing of S.aureus by human neutrophils. Acts by binding and stabilizing human C3 convertases (C4b2a and C3bBb), leading to their inactivation. The convertases are no longer able to cleave complement C3, therefore preventing further C3b deposition on the bacterial surface and phagocytosis of the bacterium. Also prevents C5a-induced neutrophil responses.[ARBA:ARBA00025334] |
| - | To survive in immune-competent hosts, the pathogen Staphylococcus aureus expresses and secretes a sophisticated array of proteins that inhibit the complement system. Among these are the staphylococcal complement inhibitors (SCIN), which are composed of three active proteins (SCIN-A, -B, and -C) and one purportedly inactive member (SCIN-D or ORF-D). Because previous work has focused almost exclusively on SCIN-A, we sought to provide initial structure/function information on additional SCIN proteins. To this end we determined crystal structures of an active, N-terminal truncation mutant of SCIN-B (denoted SCIN-B(18-85)) both free and bound to the C3c fragment of complement component C3 at 1.5 and 3.4 A resolution, respectively. Comparison of the C3c/SCIN-B(18-85) structure with that of C3c/SCIN-A revealed that both proteins target the same functional hotspot on the C3b/C3c surface yet harbor diversity in both the type of residues and interactions formed at their C3b/C3c interfaces. Most importantly, these structures allowed identification of Arg(44) and Tyr(51) as residues key for SCIN-B binding to C3b and subsequent inhibition of the AP C3 convertase. In addition, we also solved several crystal structures of SCIN-D to 1.3 A limiting resolution. This revealed an unexpected structural deviation in the N-terminal alpha helix relative to SCIN-A and SCIN-B. Comparative analysis of both electrostatic potentials and surface complementarity suggest a physical explanation for the inability of SCIN-D to bind C3b/C3c. Together, these studies provide a more thorough understanding of immune evasion by S. aureus and enhance potential use of SCIN proteins as templates for design of complement targeted therapeutics.
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| - | Diversity in the C3b Convertase Contact Residues and Tertiary Structures of the Staphylococcal Complement Inhibitor (SCIN) Protein Family.,Garcia BL, Summers BJ, Lin Z, Ramyar KX, Ricklin D, Kamath DV, Fu ZQ, Lambris JD, Geisbrecht BV J Biol Chem. 2012 Jan 2;287(1):628-40. Epub 2011 Nov 15. PMID:22086928<ref>PMID:22086928</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 3t47" style="background-color:#fffaf0;"></div>
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| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Staam]] | + | [[Category: Large Structures]] |
| - | [[Category: Garcia, B L]] | + | [[Category: Staphylococcus aureus subsp. aureus Mu50]] |
| - | [[Category: Geisbrecht, B V]] | + | [[Category: Garcia BL]] |
| - | [[Category: Summers, B J]] | + | [[Category: Geisbrecht BV]] |
| - | [[Category: Immune system]] | + | [[Category: Summers BJ]] |
| - | [[Category: Secreted]]
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| - | [[Category: Virulence]]
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