HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Baker, M. Articles by Acharya, K. R. Search for Related Content PubMed PubMed Citation Articles by Baker, M. Articles by Acharya, K. R. Social Bookmarking                   What's this?

FOR THE RECORD

Structural features of a zinc binding site in the superantigen strepococcal pyrogenic exotoxin A (SpeA1): Implications for MHC class II recognition

¹ Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom
² Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida 33101, USA

Reprint requests to: K. Ravi Acharya, Department of Biology and Biochemistry, South Building, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom; e-mail: K.R.Acharya{at}bath.ac.uk; fax: +44-1225-826-779.

Streptococcal pyrogenic exotoxin A (SpeA) is produced by Streptococcus pyogenes, and has been associated with severe infections such as scarlet fever and Streptococcal Toxic Shock Syndrome (STSS). In this study, the crystal structure of SpeA1 (the product of speA allele 1) in the presence of 2.5 mM zinc was determined at 2.8 Å resolution. The protein crystallizes in the orthorhombic space group P2₁2₁2, with four molecules in the crystallographic asymmetric unit. The final structure has a crystallographic R-factor of 21.4% for 7,031 protein atoms, 143 water molecules, and 4 zinc atoms (one zinc atom per molecule). Four protein ligands—Glu 33, Asp 77, His 106, and His 110—form a zinc binding site that is similar to the one observed in a related superantigen, staphylococcoal enterotoxin C2. Mutant toxin forms substituting Ala for each of the zinc binding residues were generated. The affinity of these mutants for zinc ion confirms the composition of this metal binding site. The implications of zinc binding to SpeA1 for MHC class II recognition are explored using a molecular modeling approach. The results indicate that, despite their common overall architecture, superantigens appear to have multiple ways of complex formation with MHC class II molecules.

Keywords: Molecular recognition; X-ray crystallography; superantigen; pyrogenic exotoxin; zinc binding

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Li, Y. Zhao, Y. Guo, Z. Li, L. Eisele, and W. Mourad Zinc Induces Dimerization of the Class II Major Histocompatibility Complex Molecule That Leads to Cooperative Binding to a Superantigen J. Biol. Chem., March 2, 2007; 282(9): 5991 - 6000. [Abstract] [Full Text] [PDF]

				D. D. Pless, G. Ruthel, E. K. Reinke, R. G. Ulrich, and S. Bavari Persistence of Zinc-Binding Bacterial Superantigens at the Surface of Antigen-Presenting Cells Contributes to the Extreme Potency of These Superantigens as T-Cell Activators Infect. Immun., September 1, 2005; 73(9): 5358 - 5366. [Abstract] [Full Text] [PDF]

				M. D. Baker, I. Gendlina, C. M. Collins, and K. R. Acharya Crystal structure of a dimeric form of streptococcal pyrogenic exotoxin A (SpeA1) Protein Sci., September 1, 2004; 13(9): 2285 - 2290. [Abstract] [Full Text] [PDF]

				M. Llewelyn, S. Sriskandan, M. Peakman, D. R. Ambrozak, D. C. Douek, W. W. Kwok, J. Cohen, and D. M. Altmann HLA Class II Polymorphisms Determine Responses to Bacterial Superantigens J. Immunol., February 1, 2004; 172(3): 1719 - 1726. [Abstract] [Full Text] [PDF]