Crystal Structure of Staphylococcal Enterotoxin G (SEG) in Complex with a Mouse T-cell Receptor beta Chain

MARISA M. FERNANDEZ; SANGWOO CHO; MAURICIO C. DE MARZI; MELISSA C. KERZIC; ROY A. MARIUZZA; EMILIO L. MALCHIODI

JOURNAL OF BIOLOGICAL CHEMISTRY

AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Año: 2010 p. 1189 - 1195

0021-9258

Superantigens (SAgs) are bacterial or viral toxins that bind major histocompatibility complex class II (MHC-II) molecules and T-cell receptor (TCR) in a non-conventional 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 (mVbeta8.2) and staphylococcal enterotoxin G (SEG) at 2.0 Å resolution revealed a binding site which does not conserve the “hot spots” present in mVbeta8.2-SEC2, mVbeta8.2-SEC3, mbeta8.2-SEB and mVbeta8.2-SPEA complexes. Analysis of the mVbeta8.2-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 mVbeta8.2 by SEG. This mode of interaction between SEG and mVbeta8.2 could be an adaptive advantage to bestow on the pathogen a faster rate of colonization of the host.