3W2D: Crystal Structure Of Staphylococcal Eenterotoxin B In Complex With A Novel Neutralization Monoclonal Antibody Fab Fragment

Citation:
Abstract
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.
PDB ID: 3W2DDownload
MMDB ID: 116164
PDB Deposition Date: 2012/11/28
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 3.1  Å
Source Organism:
Mus musculus
Similar Structures:
Biological Unit for 3W2D: trimeric; determined by author and by software (PISA)
Molecular Components in 3W2D
Label Count Molecule
Proteins (3 molecules)
1
Enterotoxin Type B
Molecule annotation
1
Monoclonal Antibody 3E2 FAB Figment Light Chain
Molecule annotation
1
Monoclonal Antibody 3E2 FAB Figment Heavy Chain
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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