title: Zinc induces dimerization of the class II major histocompatibility complex molecule that leads to cooperative binding to a superantigen.
abstract: 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.
authors.affiliation: Wadsworth Center, New York State Department of Health, University of Albany, State University of New York, Albany, New York 12208, USA. lih@wadsworth.org
authors.forename: Hongmin
authors.initials: H
authors.lastname: Li
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yi
authors.initials: Y
authors.lastname: Guo
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Leslie
authors.initials: L
authors.lastname: Eisele
authors.forename: Walid
authors.initials: W
authors.lastname: Mourad
mesh_terms: D000942:Antigens, Bacterial / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D019281:Dimerization; D015798:HLA-DR1 Antigen / Q000737:chemistry* / Q000378:metabolism; D006388:Hemagglutinins / Q000737:chemistry / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry; D045645:Mycoplasma arthritidis / Q000737:chemistry / Q000276:immunology; D011485:Protein Binding; D011487:Protein Conformation; D018089:Superantigens / Q000737:chemistry* / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology*
chemical_list: D000942:Antigens, Bacterial; D015798:HLA-DR1 Antigen; D006388:Hemagglutinins; D000949:Histocompatibility Antigens Class II; D046912:Multiprotein Complexes; C052996:Mycoplasma arthritidis mitogen; D018089:Superantigens; D015032:Zinc