Zinc induces dimerization of the class II major histocompatibility complex molecule that leads to cooperative binding to a superantigen

J Biol Chem. 2007 Mar 2;282(9):5991-6000. doi: 10.1074/jbc.M608482200. Epub 2006 Dec 13.


Dimerization of class II major histocompatibility complex (MHC) plays an important role in the MHC biological function. Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing specific T cell receptor Vbeta elements. Here we have used structural, sedimentation, and surface plasmon resonance detection approaches to investigate the molecular interactions between MAM and the class II MHC molecule HLA-DR1 in the context of a hemagglutinin peptide-(306-318) (HA). Our results revealed that zinc ion can efficiently induce the dimerization of the HLA-DR1/HA complex. Because the crystal structure of the MAM/HLA-DR1/hemagglutinin complex in the presence of EDTA is nearly identical to the structure of the complex crystallized in the presence of zinc ion, Zn(2+) is evidently not directly involved in the binding between MAM and HLA-DR1. Sedimentation and surface plasmon resonance studies further revealed that MAM binds the HLA-DR1/HA complex with high affinity in a 1:1 stoichiometry, in the absence of Zn(2+). However, in the presence of Zn(2+), a dimerized MAM/HLA-DR1/HA complex can arise through the Zn(2+)-induced DR1 dimer. In the presence of Zn(2+), cooperative binding of MAM to the DR1 dimer was also observed.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, Bacterial / chemistry*
  • Antigens, Bacterial / metabolism
  • Crystallography, X-Ray
  • Dimerization
  • HLA-DR1 Antigen / chemistry*
  • HLA-DR1 Antigen / metabolism
  • Hemagglutinins / chemistry
  • Hemagglutinins / metabolism
  • Histocompatibility Antigens Class II / chemistry
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Multiprotein Complexes / chemistry
  • Mycoplasma arthritidis / chemistry
  • Mycoplasma arthritidis / immunology
  • Protein Binding
  • Protein Conformation
  • Superantigens / chemistry*
  • Superantigens / metabolism
  • Zinc / pharmacology*


  • Antigens, Bacterial
  • HLA-DR1 Antigen
  • Hemagglutinins
  • Histocompatibility Antigens Class II
  • Multiprotein Complexes
  • Mycoplasma arthritidis mitogen
  • Superantigens
  • Zinc

Associated data

  • PDB/2OJE