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4rgn

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Revision as of 06:55, 2 March 2023

Structure of Staphylococcal Enterotoxin B bound to two neutralizing antibodies, 14G8 and 6D3

Structural highlights

4rgn is a 10 chain structure with sequence from Mus musculus and Staphylococcus aureus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ETXB_STAAU Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness characterized by high fever, hypotension, diarrhea, shock, and in some cases death.

Publication Abstract from PubMed

Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major histocompatibility complex class-II (MHC- II) and specific V-beta chains of the T-cell receptor (TCR) thus forming a ternary complex. Developing neutralizing monoclonal antibodies (mAb) to disrupt the ternary complex and abrogate the resulting toxicity is a major therapeutic challenge because SEB is effective at very low concentrations. We show that combining two SEB-specific mAbs enhances their efficacy even though one of the two mAbs by itself has no effect on neutralization. Crystallography was employed for fine- mapping of conformational epitopes in binary and ternary complexes between SEB and Fab fragments. NMR spectroscopy was used to validate and identify subtle allosteric changes induced by mAbs-binding to SEB. The mapping of epitopes established that combination of different mAbs can enhance efficacy of mAb-mediated protection from SEB induced lethal shock by two different mechanisms: one mAb cocktail promoted clearance of the toxin both in vitro and in vivo by FcR mediated crosslinking and clearance; whereas the other mAb cocktail induced subtle allosteric conformational changes in SEB that perturbed formation of the SEB:TCR:MHC-II trimer. Finally structural information accurately predicted mAb binding to other superantigens that share conformational epitopes with SEB. Fine mapping of conformational epitopes is a powerful tool to establish the mechanism and optimize the action of synergistic mAb combinations.

Mechanisms mediating enhanced neutralization efficacy of staphyloccoccal enterotoxin B by combinations of monoclonal antibodies.,Dutta K, Varshney AK, Franklin MC, Goger M, Wang X, Fries BC J Biol Chem. 2015 Jan 8. pii: jbc.M114.630715. PMID:25572397^[1]

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

References

↑ Dutta K, Varshney AK, Franklin MC, Goger M, Wang X, Fries BC. Mechanisms mediating enhanced neutralization efficacy of staphyloccoccal enterotoxin B by combinations of monoclonal antibodies. J Biol Chem. 2015 Jan 8. pii: jbc.M114.630715. PMID:25572397 doi:http://dx.doi.org/10.1074/jbc.M114.630715

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4rgn"

@@ Line 3: / Line 3: @@
 <StructureSection load='4rgn' size='340' side='right'caption='[[4rgn]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4rgn]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885] and [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RGN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RGN FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4rgn]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RGN FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4rgm|4rgm]], [[4rgo|4rgo]]</td></tr>
+</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=4rgn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rgn OCA], [https://pdbe.org/4rgn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rgn RCSB], [https://www.ebi.ac.uk/pdbsum/4rgn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rgn ProSAT]</span></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">entB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</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=4rgn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rgn OCA], [http://pdbe.org/4rgn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rgn RCSB], [http://www.ebi.ac.uk/pdbsum/4rgn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4rgn ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/ETXB_STAAU ETXB_STAAU]] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness characterized by high fever, hypotension, diarrhea, shock, and in some cases death.
+[https://www.uniprot.org/uniprot/ETXB_STAAU ETXB_STAAU] Staphylococcal enterotoxins cause the intoxication staphylococcal food poisoning syndrome. The illness characterized by high fever, hypotension, diarrhea, shock, and in some cases death.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 17: @@
 </div>
 <div class="pdbe-citations 4rgn" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
 == References ==
 <references/>
@@ Line 25: / Line 26: @@
 [[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Dutta, K]]
+[[Category: Staphylococcus aureus]]
-[[Category: Franklin, M C]]
+[[Category: Dutta K]]
-[[Category: Fries, B C]]
+[[Category: Franklin MC]]
-[[Category: Goger, M J]]
+[[Category: Fries BC]]
-[[Category: Varshney, A K]]
+[[Category: Goger MJ]]
-[[Category: Neutralizing antibody]]
+[[Category: Varshney AK]]
-[[Category: Staphylococcal enterotoxin b]]
-[[Category: Toxin-immune system complex]]

4rgn

From Proteopedia

Revision as of 06:55, 2 March 2023

Structure of Staphylococcal Enterotoxin B bound to two neutralizing antibodies, 14G8 and 6D3

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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