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

Baker, M Gutman, DM Papageorgiou, AC Collins, CM Acharya, KR

M. Baker et al., Structural features of a zinc binding site in the superantigen streptococcal pyrogenic exotoxin A (SpeA1): Implications for MHC class IT recognition, PROTEIN SCI, 10(6), 2001, pp. 1268-1273

31

INGLESE

Article

Biochemistry & Biophysics

PROTEIN SCIENCE

0961-8368 → ACNP

10

6

2001

1268 - 1273

ISI

0961-8368(200106)10:6<1268:SFOAZB>2.0.ZU;2-Q

Streptococcal pyrogenic exotoxin A (SpeA) is produced by Streptococcus pyog enes, and has been associated with severe infections such as scarlet fever and Streptococcal Toxic Shock Syndrome (STSS). In this study, the crystal s tructure of SpeA1 (the product of speA allele 1) in the presence of 2.5 mM zinc was determined at 2.8 Angstrom resolution. The protein crystallizes in the orthorhombic space group P2(1)2(1)2, with four molecules in the crysta llographic asymmetric unit. The final structure has a crystallographic R-fa ctor of 21.4% for 7,031 protein atoms, 143 water molecules, and 4 zinc atom s tone zinc atom per molecule). Four protein ligands-Glu 33, Asp 77, His 10 6, and His 110-form a zinc binding site that is similar to the one observed in a related superantigen, staphylococcoal enterotoxin C2. Mutant toxin fo rms 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 clas s ii recognition are explored using a molecular modeling approach. The resu lts indicate that, despite their common overall architecture, superantigens appear to have multiple ways of complex formation with MHC class II molecu les.