Structural and functional role of threonine 112 in a superantigen Staphylococcus aureus enterotoxin B.
Bacterial superantigens are potent T-cell stimulatory protein molecules produced by Staphylococcus aureus and Streptococcus pyogenes. Their superantigenic activity can be attributed to their ability to cross-link major histocompatibility complex class II molecules with T-cell receptors (TCRs) to form a tri-molecular complex. Each superantigen is known to interact with a specific V(beta) element of TCR. Staphylococcal enterotoxin B (SEB, a superantigen), a primary cause of food poisoning, is also responsible for a significant percentage of non-menstrual associated toxic shock syndrome in patients with a variety of staphylococcal infections. Structural studies have elucidated a binding cavity on the toxin molecule essential for TCR binding. To understand the crucial residues involved in binding, mutagenesis analysis was performed. Our analysis suggest that mutation of a conserved residue Thr(112) to Ser (T112S) in the binding cavity induces a selective reduction in the affinity for binding one TCR V(beta) family and can be attributed to the structural differences in the native and mutant toxins. We present a detailed comparison of the mutant structure determined at 2.0 A with the previously reported native SEB and SEB-TCR V(beta) complex structures.
Baker
Matthew D
MD
Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom.
Papageorgiou
Anastassios C
AC
Titball
Richard W
RW
Miller
Julie
J
White
Sarah
S
Lingard
Bryan
B
Lee
Jeong Jin
JJ
Cavanagh
David
D
Kehoe
Michael A
MA
Robinson
John H
JH
Acharya
K Ravi
KR
D000596:Amino Acids / Q000737:chemistry; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry*; D005434:Flow Cytometry; D005802:Genes, MHC Class II; D006801:Humans; D008285:Major Histocompatibility Complex; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D013912:Threonine / Q000737:chemistry* / Q000502:physiology*
D000596:Amino Acids; D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013912:Threonine; C031818:enterotoxin B, staphylococcal