Crystal structure of staphylococcal enterotoxin G (SEG) in complex with a mouse T-cell receptor {beta} chain.
Superantigens (SAgs) are bacterial or viral toxins that bind MHC class II (MHC-II) molecules and T-cell receptor (TCR) in a nonconventional manner, inducing T-cell activation that leads to inflammatory cytokine production, which may result in acute toxic shock. In addition, the emerging threat of purpura fulminans and community-associated meticillin-resistant Staphylococcus aureus emphasizes the importance of a better characterization of SAg binding to their natural ligands that may allow the development of reagents to neutralize their action. The three-dimensional structure of the complex between a mouse TCR β chain (mVβ8.2) and staphylococcal enterotoxin G (SEG) at 2.0 Å resolution revealed a binding site that does not conserve the "hot spots" present in mVβ8.2-SEC2, mVβ8.2-SEC3, mVβ8.2-SEB, and mVβ8.2-SPEA complexes. Analysis of the mVβ8.2-SEG interface allowed us to explain the higher affinity of this complex compared with the others, which may account for the early activation of T-cells bearing mVβ8.2 by SEG. This mode of interaction between SEG and mVβ8.2 could be an adaptive advantage to bestow on the pathogen a faster rate of colonization of the host.
Cátedra de Inmunología and Instituto de Estudios de la Inmunidad Humoral Prof Ricardo A. Margni, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956 4to P, 1113 Buenos Aires, Argentina.
Marisa M
MM
Fernández
Sangwoo
S
Cho
Mauricio C
MC
De Marzi
Melissa C
MC
Kerzic
Howard
H
Robinson
Roy A
RA
Mariuzza
Emilio L
EL
Malchiodi
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004768:Enterotoxins / Q000737:chemistry* / Q000378:metabolism*; D004926:Escherichia coli; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000737:chemistry* / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000378:metabolism*; D013329:Structure-Activity Relationship; D018089:Superantigens / Q000737:chemistry* / Q000378:metabolism*
D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C419397:enterotoxin G, staphylococcal