5hzp

From Proteopedia

(Difference between revisions)

Revision as of 16:15, 11 December 2019

Structure of human C4b-binding protein alpha chain CCP domains 1 and 2 in complex with the hypervariable region of group A Streptococcus M49 protein.

Structural highlights

5hzp is a 4 chain structure with sequence from Human and Strp9. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Related:	5hyu, 5hyp, 5hyt, 5i0q
Gene:	emm49 (STRP9), C4BPA, C4BP (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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. [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.

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

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/5hzp"

@@ Line 1: / Line 1: @@
 ==Structure of human C4b-binding protein alpha chain CCP domains 1 and 2 in complex with the hypervariable region of group A Streptococcus M49 protein.==
-<StructureSection load='5hzp' size='340' side='right' caption='[[5hzp]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
+<StructureSection load='5hzp' size='340' side='right'caption='[[5hzp]], [[Resolution|resolution]] 2.74&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5hzp]] is a 4 chain structure. 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 [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>
 </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>
 <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='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='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>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
+[[Category: Strp9]]
 [[Category: Bahn-Suh, A J]]
 [[Category: Buffalo, C Z]]

5hzp

From Proteopedia

Revision as of 16:15, 11 December 2019

Structure of human C4b-binding protein alpha chain CCP domains 1 and 2 in complex with the hypervariable region of group A Streptococcus M49 protein.

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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