Crystal Structure of Mycoplasma arthritidis Mitogen Complexed with HLA-DR1 Reveals a Novel Superantigen Fold and a Dimerized Superantigen-MHC Complex

Yiwei Zhao, Zhong Li, Sandra J. Drozd, Yi Guo, Walid Mourad, Hongmin Li

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing particular TCR Vβ elements. Here we report the crystal structure of MAM complexed with a major histocompatibility complex (MHC) antigen, HLA-DR1, loaded with haemagglutinin peptide 306-318 (HA). The structure reveals that MAM has a novel fold composed of two α-helical domains. This fold is entirely different from that of the pyrogenic superantigens, consisting of a β-grasped motif and a β barrel. In the complex, the N-terminal domain of MAM binds orthogonally to the MHC α1 domain and the bound HA peptide, and to a lesser extent to the MHC β1 domain. Two MAM molecules form an asymmetric dimer and cross-link two MHC antigens to form a plausible, dimerized MAM-MHC complex. These data provide the first crystallographic evidence that superantigens can dimerize MHC molecules. Based on our structure, a model of the TCR2MAM 2MHC2 complex is proposed.

Original languageEnglish (US)
Pages (from-to)277-288
Number of pages12
JournalStructure
Volume12
Issue number2
DOIs
StatePublished - Feb 2004
Externally publishedYes

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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