Crystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II.

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TitleCrystal structure of a superantigen bound to the high-affinity, zinc-dependent site on MHC class II.
Publication TypeJournal Article
Year of Publication2001
AuthorsLi, Y, Li, H, Dimasi, N, McCormick, JK, Martin, R, Schuck, P, Schlievert, PM, Mariuzza, RA
JournalImmunity
Volume14
Issue1
Pagination93-104
Date Published2001 Jan
ISSN1074-7613
KeywordsAnimals, Bacterial Proteins, Binding Sites, Crystallography, X-Ray, Exotoxins, Histocompatibility Antigens Class II, HLA-DR2 Antigen, Humans, Membrane Proteins, Mice, Models, Molecular, Myelin Basic Protein, Protein Structure, Secondary, Superantigens, Zinc
Abstract

MHC class II molecules possess two binding sites for bacterial superantigens (SAGs): a low-affinity site on the alpha chain and a high-affinity, zinc-dependent site on the beta chain. Only the former has been defined crystallographically. We report the structure of streptococcal pyrogenic exotoxin C (SPE-C) complexed with HLA-DR2a (DRA*0101, DRB5*0101) bearing a self-peptide from myelin basic protein (MBP). SPE-C binds the beta chain through a zinc bridge that links the SAG and class II molecules. Surprisingly, SPE-C also makes extensive contacts with the MBP peptide, such that peptide accounts for one third of the surface area of the MHC molecule buried in the complex, similar to TCR-peptide/MHC complexes. Thus, SPE-C may optimize T cell responses by mimicking the peptide dependence of conventional antigen presentation and recognition.

Alternate JournalImmunity
PubMed ID11163233
Grant List36611 / / PHS HHS / United States
AI36900 / AI / NIAID NIH HHS / United States
AI42937 / AI / NIAID NIH HHS / United States