2ICI

Crystal Structure of Streptococcal Pyrogenic Exotoxin I

Summary for 2ICI

• Entry DOI: 10.2210/pdb2ici/pdb
• Descriptor: Exotoxin I, MAGNESIUM ION (3 entities in total)
• Functional Keywords: streptococcal superantigen spei, toxin
• Biological source: Streptococcus pyogenes
• Total number of polymer chains: 1
• Total formula weight: 26275.84

Authors

Gunther, S.,Varma, A.K.,Sundberg, E.J. (deposition date: 2006-09-12, release date: 2007-03-27, Last modification date: 2024-10-30)

Primary citation

Brouillard, J.N.,Gunther, S.,Varma, A.K.,Gryski, I.,Herfst, C.A.,Rahman, A.K.,Leung, D.Y.,Schlievert, P.M.,Madrenas, J.,Sundberg, E.J.,McCormick, J.K.
Crystal Structure of the Streptococcal Superantigen SpeI and Functional Role of a Novel Loop Domain in T Cell Activation by Group V Superantigens.
J.Mol.Biol., 367:925-934, 2007

PubMed 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 approximately 15 amino acid extension (amino acid residues 154 to 170 in SpeI; herein referred to as the alpha3-beta8 loop), absent in SAg groups I through IV. Here, we report the crystal structure of SpeI at 1.56 A resolution. Although the alpha3-beta8 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 beta-chains are likely engaged in a similar general orientation as other characterized SAgs. We show, however, that the alpha3-beta8 loop length, and the presence of key glycine residues, are necessary for optimal activation of T cells. Based on Vbeta-skewing analysis of human T cells activated with SpeI and structural models, we propose that the alpha3-beta8 loop is positioned to form productive intermolecular contacts with the TCR beta-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.

PubMed: 17303163
DOI: 10.1016/j.jmb.2007.01.024

Experimental method

X-RAY DIFFRACTION (1.56 Å)