1r5i Citations

Crystal structure of Mycoplasma arthritidis mitogen complexed with HLA-DR1 reveals a novel superantigen fold and a dimerized superantigen-MHC complex.

Structure 12 277-88 (2004)
Cited: 15 times
EuropePMC logo PMID: 14962388


Mycoplasma arthritidis-derived mitogen (MAM) is a superantigen that can activate large fractions of T cells bearing particular TCR Vbeta 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 alpha-helical domains. This fold is entirely different from that of the pyrogenic superantigens, consisting of a beta-grasped motif and a beta barrel. In the complex, the N-terminal domain of MAM binds orthogonally to the MHC alpha1 domain and the bound HA peptide, and to a lesser extent to the MHC beta1 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 TCR2MAM2MHC2 complex is proposed.

Articles - 1r5i mentioned but not cited (1)

Reviews citing this publication (2)

  1. Toxins from bacteria. Henkel JS, Baldwin MR, Barbieri JT. EXS 100 1-29 (2010)
  2. Narcolepsy: autoimmunity, effector T cell activation due to infection, or T cell independent, major histocompatibility complex class II induced neuronal loss? Fontana A, Gast H, Reith W, Recher M, Birchler T, Bassetti CL. Brain 133 1300-1311 (2010)

Articles citing this publication (12)

  1. The landscape of human proteins interacting with viruses and other pathogens. Dyer MD, Murali TM, Sobral BW. PLoS Pathog. 4 e32 (2008)
  2. Crystal structure of a complete ternary complex of TCR, superantigen and peptide-MHC. Wang L, Zhao Y, Li Z, Guo Y, Jones LL, Kranz DM, Mourad W, Li H. Nat. Struct. Mol. Biol. 14 169-171 (2007)
  3. Cloning, expression and interaction of human T-cell receptors with the bacterial superantigen SSA. De Marzí MC, Fernández MM, Sundberg EJ, Molinero L, Zwirner NW, Llera AS, Mariuzza RA, Malchiodi EL. Eur. J. Biochem. 271 4075-4083 (2004)
  4. Zinc induces dimerization of the class II major histocompatibility complex molecule that leads to cooperative binding to a superantigen. Li H, Zhao Y, Guo Y, Li Z, Eisele L, Mourad W. J. Biol. Chem. 282 5991-6000 (2007)
  5. Crystal structures of T cell receptor (beta) chains related to rheumatoid arthritis. Li H, Van Vranken S, Zhao Y, Li Z, Guo Y, Eisele L, Li Y. Protein Sci. 14 3025-3038 (2005)
  6. Crucial cytokine interactions in nitric oxide production induced by Mycoplasma arthritidis superantigen. Shio MT, Olivier M, Jancar S, Ribeiro-Dias F. Microbes Infect. 10 1543-1551 (2008)
  7. Mutagenesis, biochemical, and biophysical characterization of Mycoplasma arthritidis-derived mitogen. Li H, Zhao Y, Guo Y, Vanvranken SJ, Li Z, Eisele L, Mourad W. Mol. Immunol. 44 763-773 (2007)
  8. 3PFDB--a database of best representative PSSM profiles (BRPs) of protein families generated using a novel data mining approach. Shameer K, Nagarajan P, Gaurav K, Sowdhamini R. BioData Min 2 8 (2009)
  9. Pfit is a structurally novel Crohn's disease-associated superantigen. Liu L, Chen H, Brecher MB, Li Z, Wei B, Nandi B, Zhang J, Ling H, Winslow G, Braun J, Li H. PLoS Pathog. 9 e1003837 (2013)
  10. A single point mutation changes the crystallization behavior of Mycoplasma arthritidis-derived mitogen. Guo Y, Li Z, Van Vranken SJ, Li H. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62 238-241 (2006)
  11. Crystal structure of Streptococcus dysgalactiae-derived mitogen reveals a zinc-binding site and alterations in TcR binding. Saarinen S, Kato H, Uchiyama T, Miyoshi-Akiyama T, Papageorgiou AC. J. Mol. Biol. 373 1089-1097 (2007)
  12. Crystal structure of the Mycoplasma arthritidis-derived mitogen in apo form reveals a 3D domain-swapped dimer. Liu L, Li Z, Guo Y, VanVranken SJ, Mourad W, Li H. J. Mol. Biol. 399 367-376 (2010)