TY - JOUR
T1 - Crystal Structure of Mycoplasma arthritidis Mitogen Complexed with HLA-DR1 Reveals a Novel Superantigen Fold and a Dimerized Superantigen-MHC Complex
AU - Zhao, Yiwei
AU - Li, Zhong
AU - Drozd, Sandra J.
AU - Guo, Yi
AU - Mourad, Walid
AU - Li, Hongmin
N1 - Funding Information:
This research is supported by a grant (AI50628) from the National Institute of Health (NIH) (to H.L.). We thank R.A. Mariuzza, G. Winslow, and P. Van Roey for critical readings of the manuscript, L.J. Stern for the gift of HLA-DR1 expression plasmids, and the Peptide Synthesis Core facility at the Wadsworth Center for the synthesis of the HA peptide. We thank R.G. Zhang at APS, and R. Sweet and M. Becker at NSLS for assistance in X-ray data collection. The X-ray diffraction facilities at the APS and NSLS are supported by the Department of Energy and by grants from NIH.
PY - 2004/2
Y1 - 2004/2
N2 - 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.
AB - 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.
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U2 - 10.1016/S0969-2126(04)00020-6
DO - 10.1016/S0969-2126(04)00020-6
M3 - Article
C2 - 14962388
AN - SCOPUS:1242306188
SN - 0969-2126
VL - 12
SP - 277
EP - 288
JO - Structure
JF - Structure
IS - 2
ER -