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. 2001 Jul 2;20(13):3306-12.
doi: 10.1093/emboj/20.13.3306.

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

K Petersson  1 , M Håkansson, H Nilsson, G Forsberg, L A Svensson, A Liljas, B Walse
Affiliations

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

K Petersson et al. EMBO J. .

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 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 affinity through a zinc ion with the beta1 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.

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Figures

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Fig. 1. Gel filtration analyses of the HLA-DR1 complex, measuring the fluorescence. (A) SEH, (B) the HLA-DR1–peptide complex, (C) SEH and the HLA-DR1–peptide complex in the presence of zinc, and (D) SEH and the HLA-DR1–peptide complex in the presence of EDTA.
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Fig. 2. Ribbon representation of the HLA-DR1–SEH complex with HLA-DR1 (green), HA-peptide (red) and SEH (yellow).
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Fig. 3. Surface representation of HLA-DR1 (grey) with the residues involved in hydrogen bonding to SEH marked in green. The β-sheets on SEH (β6, β7, β9, β10 and β12) that are interacting with HLA-DR1 are drawn in yellow and the antigen peptide is in red. Side chains on SEH forming hydrogen bonds are coloured orange.
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Fig. 4. The coordination and hydrogen bond pattern of selected residues in the region around the zinc ion (magenta) and the HA-peptide (grey)–HLA-DR1 (green)–SEH (yellow) complex. An additional hydrogen bond between Asp208s, OD1 and Asn113s, ND2 (2.7 Å) is observed but omitted in the picture for clarity.
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Fig. 5. Electron density from the final 2.6 Å 2Fo – Fc map of the HA-peptide–SEH interaction, contoured at 1σ, with the HA-peptide (green) and SEH (yellow). Gln120s forms a bidentate hydrogen bond with Lys310p (p3).
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Fig. 6. Sequence alignment of the zinc family of superantigens and SEB. Residues involved in the HLA-DR1–SEH interaction are marked in yellow. Numbering is according to SEH. The N-terminal parts of the sequences are not shown.
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Fig. 7. Comparison between the HLA-DR2a–MBP peptide–SPE-C complex (Li et al., 2001, 1HQR) and the HLA-DR1–HA-peptide–SEH complex. The superposition was made by fitting the α-chains of the HLA-DRs to each other. The MBP peptide is marked in cyan, the HA-peptide in red, SEH in yellow and SPE-C in blue. The β-chain of HLA-DR1 is represented as a surface (grey).
See this image and copyright information in PMC

References

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