3w2d: Difference between revisions
No edit summary |
No edit summary |
||
| (6 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
The | ==Crystal Structure of Staphylococcal Eenterotoxin B in complex with a novel neutralization monoclonal antibody Fab fragment== | ||
<StructureSection load='3w2d' size='340' side='right'caption='[[3w2d]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3w2d]] is a 3 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=3W2D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3W2D 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]] 3.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=3w2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3w2d OCA], [https://pdbe.org/3w2d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3w2d RCSB], [https://www.ebi.ac.uk/pdbsum/3w2d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3w2d 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 (SE) B is among the potent toxins produced by Staphylococcus aureus that cause toxic shock syndrome (TSS), which can result in multi-organ failure and death. Currently, neutralizing antibodies have been shown to be effective immunotherapeutic agents against this toxin, but the structural basis of the neutralizing mechanism is still unknown. In this study, we generated a neutralizing monoclonal antibody, 3E2, against SEB, and analyzed the crystal structure of the SEB-3E2 Fab complex. Crystallographic analysis suggested that the neutralizing epitope overlapped with the MHC II molecule binding site on SEB, and thus 3E2 could inhibit SEB function by preventing interaction with the MHC II molecule. Mutagenesis studies were done on SEB, as well as the related Staphylococcus aureus toxins SEA and SEC. These studies revealed that tyrosine (Y)46 and lysine (K)71 residues of SEB are essential to specific antibody-antigen recognition and neutralization. Substitution of Y at SEA glutamine (Q)49, which corresponds to SEB Y46, increased both 3E2's binding to SEA in vitro and the neutralization of SEA in vivo. These results suggested that SEB Y46 is responsible for distinguishing SEB from SEA. These findings may be helpful for the development of antibody-based therapy for SEB-induced TSS. | |||
Structural basis for the neutralization and specificity of Staphylococcal enterotoxin B against its MHC Class II binding site.,Xia T, Liang S, Wang H, Hu S, Sun Y, Yu X, Han J, Li J, Guo S, Dai J, Lou Z, Guo Y MAbs. 2014 Jan-Feb;6(1):119-29. doi: 10.4161/mabs.27106. PMID:24423621<ref>PMID:24423621</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3w2d" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Staphylococcus aureus]] | |||
[[Category: Dai JX]] | |||
[[Category: Guo YJ]] | |||
[[Category: Hu S]] | |||
[[Category: Liang SY]] | |||
[[Category: Lou ZY]] | |||
Latest revision as of 12:50, 30 October 2024
Crystal Structure of Staphylococcal Eenterotoxin B in complex with a novel neutralization monoclonal antibody Fab fragmentCrystal Structure of Staphylococcal Eenterotoxin B in complex with a novel neutralization monoclonal antibody Fab fragment
Structural highlights
FunctionETXB_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 PubMedStaphylococcal enterotoxin (SE) B is among the potent toxins produced by Staphylococcus aureus that cause toxic shock syndrome (TSS), which can result in multi-organ failure and death. Currently, neutralizing antibodies have been shown to be effective immunotherapeutic agents against this toxin, but the structural basis of the neutralizing mechanism is still unknown. In this study, we generated a neutralizing monoclonal antibody, 3E2, against SEB, and analyzed the crystal structure of the SEB-3E2 Fab complex. Crystallographic analysis suggested that the neutralizing epitope overlapped with the MHC II molecule binding site on SEB, and thus 3E2 could inhibit SEB function by preventing interaction with the MHC II molecule. Mutagenesis studies were done on SEB, as well as the related Staphylococcus aureus toxins SEA and SEC. These studies revealed that tyrosine (Y)46 and lysine (K)71 residues of SEB are essential to specific antibody-antigen recognition and neutralization. Substitution of Y at SEA glutamine (Q)49, which corresponds to SEB Y46, increased both 3E2's binding to SEA in vitro and the neutralization of SEA in vivo. These results suggested that SEB Y46 is responsible for distinguishing SEB from SEA. These findings may be helpful for the development of antibody-based therapy for SEB-induced TSS. Structural basis for the neutralization and specificity of Staphylococcal enterotoxin B against its MHC Class II binding site.,Xia T, Liang S, Wang H, Hu S, Sun Y, Yu X, Han J, Li J, Guo S, Dai J, Lou Z, Guo Y MAbs. 2014 Jan-Feb;6(1):119-29. doi: 10.4161/mabs.27106. PMID:24423621[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||