4rgn: Difference between revisions

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'''Unreleased structure'''


The entry 4rgn is ON HOLD  until Paper Publication
==Structure of Staphylococcal Enterotoxin B bound to two neutralizing antibodies, 14G8 and 6D3==
<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 [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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.698&#8491;</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>
</table>
== Function ==
[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 ==
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.


Authors: Franklin, M.C., Dutta, K., Varshney, A.K., Goger, M.J., Fries, B.C.
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<ref>PMID:25572397</ref>


Description: Structure of Staphylococcal Enterotoxin B bound to two neutralizing antibodies, 14G8 and 6D3
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Franklin, M.C]]
<div class="pdbe-citations 4rgn" style="background-color:#fffaf0;"></div>
[[Category: Fries, B.C]]
 
[[Category: Goger, M.J]]
==See Also==
[[Category: Dutta, K]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
[[Category: Varshney, A.K]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Staphylococcus aureus]]
[[Category: Dutta K]]
[[Category: Franklin MC]]
[[Category: Fries BC]]
[[Category: Goger MJ]]
[[Category: Varshney AK]]
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