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| | <StructureSection load='5hzp' size='340' side='right'caption='[[5hzp]], [[Resolution|resolution]] 2.74Å' scene=''> | | <StructureSection load='5hzp' size='340' side='right'caption='[[5hzp]], [[Resolution|resolution]] 2.74Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hzp]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Strp9 Strp9]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HZP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HZP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hzp]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Streptococcus_pyogenes_serotype_M49 Streptococcus pyogenes serotype M49]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HZP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2.74Å</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=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5hyu|5hyu]], [[5hyp|5hyp]], [[5hyt|5hyt]], [[5i0q|5i0q]]</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=5hzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hzp OCA], [https://pdbe.org/5hzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hzp RCSB], [https://www.ebi.ac.uk/pdbsum/5hzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hzp ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">emm49 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=301452 STRP9]), C4BPA, C4BP ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5hzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hzp OCA], [http://pdbe.org/5hzp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hzp RCSB], [http://www.ebi.ac.uk/pdbsum/5hzp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hzp ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/M49_STRP9 M49_STRP9]] This protein is one of the different antigenic serotypes of protein M. Protein M is closely associated with virulence of the bacterium and can render the organism resistant to phagocytosis. [[http://www.uniprot.org/uniprot/C4BPA_HUMAN C4BPA_HUMAN]] Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. Alpha chain binds C4b. It interacts also with anticoagulant protein S and with serum amyloid P component. | + | [https://www.uniprot.org/uniprot/M49_STRP9 M49_STRP9] This protein is one of the different antigenic serotypes of protein M. Protein M is closely associated with virulence of the bacterium and can render the organism resistant to phagocytosis. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Strp9]] | + | [[Category: Streptococcus pyogenes serotype M49]] |
| - | [[Category: Bahn-Suh, A J]] | + | [[Category: Bahn-Suh AJ]] |
| - | [[Category: Buffalo, C Z]] | + | [[Category: Buffalo CZ]] |
| - | [[Category: Ghosh, P]] | + | [[Category: Ghosh P]] |
| - | [[Category: Compliment]]
| + | |
| - | [[Category: Hypervariable antigen]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: M protein]]
| + | |
| - | [[Category: Streptococcus pyogene]]
| + | |
| Structural highlights
Function
M49_STRP9 This protein is one of the different antigenic serotypes of protein M. Protein M is closely associated with virulence of the bacterium and can render the organism resistant to phagocytosis.
Publication Abstract from PubMed
No vaccine exists against group A Streptococcus (GAS), a leading cause of worldwide morbidity and mortality. A severe hurdle is the hypervariability of its major antigen, the M protein, with >200 different M types known. Neutralizing antibodies typically recognize M protein hypervariable regions (HVRs) and confer narrow protection. In stark contrast, human C4b-binding protein (C4BP), which is recruited to the GAS surface to block phagocytic killing, interacts with a remarkably large number of M protein HVRs (apparently approximately 90%). Such broad recognition is rare, and we discovered a unique mechanism for this through the structure determination of four sequence-diverse M proteins in complexes with C4BP. The structures revealed a uniform and tolerant 'reading head' in C4BP, which detected conserved sequence patterns hidden within hypervariability. Our results open up possibilities for rational therapies that target the M-C4BP interaction, and also inform a path towards vaccine design.
Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein.,Buffalo CZ, Bahn-Suh AJ, Hirakis SP, Biswas T, Amaro RE, Nizet V, Ghosh P Nat Microbiol. 2016 Sep 5:16155. doi: 10.1038/nmicrobiol.2016.155. PMID:27595425[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Buffalo CZ, Bahn-Suh AJ, Hirakis SP, Biswas T, Amaro RE, Nizet V, Ghosh P. Conserved patterns hidden within group A Streptococcus M protein hypervariability recognize human C4b-binding protein. Nat Microbiol. 2016 Sep 5:16155. doi: 10.1038/nmicrobiol.2016.155. PMID:27595425 doi:http://dx.doi.org/10.1038/nmicrobiol.2016.155
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