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PDBsum entry 4rgo
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Toxin/immune system
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PDB id
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4rgo
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Contents |
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225 a.a.
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213 a.a.
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212 a.a.
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PDB id:
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Toxin/immune system
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Title:
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Structure of staphylococcal enterotoxin b bound to the neutralizing antibody 14g8
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Structure:
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Enterotoxin type b. Chain: s. Fragment: unp residues 28-266. Synonym: seb, staphylococcal enterotoxin b. Engineered: yes. 14g8 heavy chain. Chain: h. Fragment: fab. 14g8 light chain.
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Source:
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Staphylococcus aureus. Organism_taxid: 1280. Gene: entb. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Mus musculus. Mouse. Organism_taxid: 10090. Cell: hybridoma.
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Resolution:
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1.80Å
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R-factor:
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0.144
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R-free:
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0.189
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Authors:
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M.C.Franklin,K.Dutta,A.K.Varshney,M.J.Goger,B.C.Fries
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Key ref:
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K.Dutta
et al.
(2015).
Mechanisms mediating enhanced neutralization efficacy of staphylococcal enterotoxin B by combinations of monoclonal antibodies.
J Biol Chem,
290,
6715-6730.
PubMed id:
DOI:
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Date:
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30-Sep-14
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Release date:
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21-Jan-15
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PROCHECK
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Headers
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References
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P01552
(ETXB_STAAU) -
Enterotoxin type B from Staphylococcus aureus
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Seq:
Struc:
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266 a.a.
225 a.a.
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DOI no:
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J Biol Chem
290:6715-6730
(2015)
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PubMed id:
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Mechanisms mediating enhanced neutralization efficacy of staphylococcal enterotoxin B by combinations of monoclonal antibodies.
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K.Dutta,
A.K.Varshney,
M.C.Franklin,
M.Goger,
X.Wang,
B.C.Fries.
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ABSTRACT
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Staphylococcal enterotoxin B (SEB) is a superantigen that cross-links the major
histocompatibility complex class II and specific V-β chains of the T-cell
receptor, thus forming a ternary complex. Developing neutralizing 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 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 a combination of different mAbs can enhance efficacy of
mAb-mediated protection from SEB induced lethal shock by two different
mechanisms: one mAb mixture promoted clearance of the toxin both in vitro and in
vivo by FcR-mediated cross-linking and clearance, whereas the other mAb mixture
induced subtle allosteric conformational changes in SEB that perturbed formation
of the SEB·T-cell receptor·major histocompatibility complex class 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.
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Links
