Streptococcus dysgalactiae-derived mitogen (SDM), a novel bacterial superantigen: characterization of its biological activity and predicted tertiary structure.
A mitogenic substance, designated Streptococcus dysgalactiae-derived mitogen (SDM), was purified from S. dysgalactiae culture supernatant, and the gene encoding the mitogen was cloned. Both native and recombinant SDM expressed in Escherichia coli significantly activated human V beta 1+ and V beta 23+ T cells in association with major histocompatibility complex (MHC) class II molecules on accessory cells, indicating that SDM possesses superantigenic properties. The sdm gene consists of two segments encoding a signal peptide and a mature 25 kDa protein composed of 212 amino acids. Three of 34 S. dysgalactiae strains but none of 28 Streptococcus pyogenes strains examined carried sdm. Phylogenetic analysis indicated that SDM belongs to a family distinct from established bacterial superantigens. SDM showed around 30% homology with other superantigens at the amino acid sequence level. The tertiary structure of SDM was predicted by modelling onto streptococcal pyrogenic exotoxin C and streptococcal mitogenic exotoxin Z-2, both of which share highly homologous structure-determining regions. SDM showed overall structural similarity to both these superantigens. This is the first study to characterize fully a bacterial superantigen from S. dysgalactiae.
Miyoshi-Akiyama
Tohru
T
Department of Microbiology and Immunology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. akiyamat@research.twmu.ac.jp
Zhao
Jizi
J
Kato
Hidehito
H
Kikuchi
Ken
K
Totsuka
Kyoichi
K
Kataoka
Yasushi
Y
Katsumi
Masanori
M
Uchiyama
Takehiko
T
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology*; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000737:chemistry; D001483:Base Sequence; D004926:Escherichia coli / Q000235:genetics; D005098:Exotoxins / Q000737:chemistry; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins; D008934:Mitogens / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D017421:Sequence Analysis; D017386:Sequence Homology, Amino Acid; D013291:Streptococcus / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D040681:Structural Homology, Protein; D018089:Superantigens / Q000737:chemistry* / Q000302:isolation & purification / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005098:Exotoxins; D000949:Histocompatibility Antigens Class II; D008565:Membrane Proteins; D008934:Mitogens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; C027951:erythrogenic toxin; C107894:mitogenic exotoxin Z protein, Streptococcus