Crystal structure of a superantigen bound to MHC class II displays zinc and peptide dependence

Abstract

The three-dimensional structure of a bacterial superantigen, Staphylococcus aureus enterotoxin H (SEH), bound to human major histocompatibility complex (MHC) class II (HLA-DR1) has been determined by X-ray crystallography to 2.6 A Ê resolution (1HXY). The superantigen binds on top of HLA-DR1 in a completely different way from earlier co-crystallized superantigens from S.aureus. SEH interacts with high af®nity through a zinc ion with the b1 chain of HLA-DR1 and also with the peptide presented by HLA-DR1. The structure suggests that all superantigens interacting with MHC class II in a zinc-dependent manner present the superantigen in a common way. This suggests a new model for ternary complex formation with the T-cell receptor (TCR), in which a contact between the TCR and the MHC class II is unlikely.

The structure of superantigen complexed with TCR and MHC reveals novel insights into superantigenic T cell activation

“…1a). The contact area between SEH and MHC is 1465 Å 2 , which correlates well with the previously published SEH-MHC structure 6 . The buried surface area between SEH and TCR is 1369 Å 2 , where TCRα contributes to 94% and TCRβ to 6%.…”

“…The class III SAgs are suggested to crosslink MHC class II molecules through a low-affinity site, as well as a high-affinity zinc-dependent site. However, the crystal structure of SEH in complex with MHC class II demonstrate that SEH interacts with MHC class II, exclusively by the high-affinity site 6 . Nevertheless, low-affinity sites for MHC may be present in SEH, but not captured in the crystal structure.…”

Mutagenesis, biochemical, and biophysical characterization of Mycoplasma arthritidis-derived mitogen

“…Zinc may regulate the SAg activity in several ways. First, the metal ion may be directly involved in the interactions between SAgs and their host receptors (Li et al, 1999(Li et al, , 2001Petersson et al, 2001). Such interactions result in a so-called "high-affinity" SAg-binding site, via a zinc bridge, on the MHC class II molecules (Hudson et al, 1995;Kozono et al, 1995;Li et al, 2001;Petersson et al, 2001).…”

“…First, the metal ion may be directly involved in the interactions between SAgs and their host receptors (Li et al, 1999(Li et al, , 2001Petersson et al, 2001). Such interactions result in a so-called "high-affinity" SAg-binding site, via a zinc bridge, on the MHC class II molecules (Hudson et al, 1995;Kozono et al, 1995;Li et al, 2001;Petersson et al, 2001). Second, some SAgs can form zinc-dependent homodimers, which could in turn cause dimerization of the MHC class II molecules on the APC surface (Al-Daccak et al, 1998;Baker et al, 2004a,b;Li et al, 1997;Papageorgiou et al, 1995Papageorgiou et al, , 2004Roussel et al, 1997;Sundstrom et al, 1996).…”

Production of recombinant proteins by sol–gel immobilized Escherichia coli

“…The interaction between SEG, produced from sol-gel immobilized bacteria, and mouse TCR ␤ chain mV␤8.2 was detected by gel filtration as described previously by Petersson et al [11] using an AKTA purifier system (Amersham Pharmacia Biotech, Upsala, Sweden). Briefly, SEG and mV␤8.2 were incubated at concentrations of 5 M for 2 h at 37 • C. The protein mixture was applied to a gel filtration S200 column equilibrated with PBS.…”