Structural Basis for the Recognition of Superantigen Streptococcal Pyrogenic Exotoxin A (SpeA1) by MHC Class II Molecules and T-cell Receptors

EMBO J. 1999 Jan 4;18(1):9-21. doi: 10.1093/emboj/18.1.9.

Abstract

Streptococcal pyrogenic exotoxin A (SpeA) is a superantigen produced by Streptococcus pyogenes and is associated with severe infections characterized by rash, hypotension, multiorgan failure and a high mortality rate. In this study, an allelic form of this toxin, SpeA1, was crystallized with four molecules in the crystallographic asymmetric unit and its crystal structure was determined at 2.6 A resolution. The crystallographic R-factor was 19.4% (33 497 reflections) for 7031 protein atoms and 88 water molecules. The overall structure of SpeA1 is considerably similar to that of other prototype microbial superantigens, either of staphylococcal or streptococcal origin, but has greatest similarity to staphylococcal enterotoxin C (SEC). Based on structural and mutagenesis data, we have mapped several important residues on the toxin molecule, which are involved in the recognition of major histocompatibility complex (MHC) class II molecules and T-cell receptors. Also, the toxin appears to possess a potential zinc-binding site which may have implications in binding to particular MHC class II molecules. Finally, we propose models for SpeA1-MHC class II and SpeA1-T-cell receptor association and the relevance of this phenomenon to the superantigenic action of this toxin is considered.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins*
  • Binding Sites
  • Crystallography, X-Ray
  • Exotoxins / chemistry*
  • Exotoxins / genetics
  • Exotoxins / immunology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Membrane Proteins*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Pyrogens / chemistry
  • Pyrogens / genetics
  • Pyrogens / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Streptococcus pyogenes / chemistry*
  • Streptococcus pyogenes / genetics
  • Streptococcus pyogenes / immunology*
  • Superantigens / chemistry*
  • Superantigens / genetics
  • T-Lymphocytes / immunology

Substances

  • Bacterial Proteins
  • Exotoxins
  • Histocompatibility Antigens Class II
  • Membrane Proteins
  • Pyrogens
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins
  • SpeA protein, Streptococcus pyogenes
  • Superantigens
  • erythrogenic toxin