Journal article
Crystal Structure of the Streptococcal Superantigen SpeI and Functional Role of a Novel Loop Domain in T Cell Activation by Group V Superantigens
Journal of molecular biology, Vol.367(4), pp.925-934
04/06/2007
DOI: 10.1016/j.jmb.2007.01.024
PMID: 17303163
Abstract
Superantigens (SAgs) are potent microbial toxins that bind simultaneously to T cell receptors (TCRs) and class II major histocompatibility complex molecules, resulting in the activation and expansion of large T cell subsets and the onset of numerous human diseases. Within the bacterial SAg family, streptococcal pyrogenic exotoxin I (SpeI) has been classified as belonging to the group V SAg subclass, which are characterized by a unique, relatively conserved ∼15 amino acid extension (amino acid residues 154 to 170 in SpeI; herein referred to as the α3–β8 loop), absent in SAg groups I through IV. Here, we report the crystal structure of SpeI at 1.56 Å resolution. Although the α3–β8 loop in SpeI is several residues shorter than that of another group V SAg, staphylococcal enterotoxin serotype I, the C-terminal portions of these loops, which are located adjacent to the putative TCR binding site, are structurally similar. Mutagenesis and subsequent functional analysis of SpeI indicates that TCR β-chains are likely engaged in a similar general orientation as other characterized SAgs. We show, however, that the α3–β8 loop length, and the presence of key glycine residues, are necessary for optimal activation of T cells. Based on Vβ-skewing analysis of human T cells activated with SpeI and structural models, we propose that the α3–β8 loop is positioned to form productive intermolecular contacts with the TCR β-chain, likely in framework region 3, and that these contacts are required for optimal TCR recognition by SpeI, and likely all other group V SAgs.
Details
- Title: Subtitle
- Crystal Structure of the Streptococcal Superantigen SpeI and Functional Role of a Novel Loop Domain in T Cell Activation by Group V Superantigens
- Creators
- Jean-Nicholas P Brouillard - Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada N6A 5B8Sebastian Günther - Boston Biomedical Research Institute, Watertown, MA 02472, USAAshok K Varma - Boston Biomedical Research Institute, Watertown, MA 02472, USAIrene Gryski - Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada N6A 5B8Christine A Herfst - Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada N6A 5B8A.K.M. Nur-ur Rahman - Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada N6A 5B8Donald Y.M Leung - Department of Pediatrics, Dermatology and Medicine, University of Colorado Health Sciences Center and Division of Pediatric Allergy and Immunology, The National Jewish Medical and Research Center, Denver, CO 80206, USAPatrick M Schlievert - Department of Microbiology, University of Minnesota Medical School, Minneapolis, MN 55455, USAJoaquín Madrenas - Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada N6A 5B8Eric J Sundberg - Boston Biomedical Research Institute, Watertown, MA 02472, USAJohn K McCormick - Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada N6A 5B8
- Resource Type
- Journal article
- Publication Details
- Journal of molecular biology, Vol.367(4), pp.925-934
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.jmb.2007.01.024
- PMID
- 17303163
- ISSN
- 0022-2836
- eISSN
- 1089-8638
- Language
- English
- Date published
- 04/06/2007
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984002395902771
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