Crystal structure of Streptococcus dysgalactiae-derived mitogen reveals a zinc-binding site and alterations in TcR binding

Bacterial superantigens are protein toxins with an ability to cause serious diseases in humans by activating a large number of T cells. Streptococcus dysgalactiae-derived mitogen (SDM) is a novel superantigen that is distinct from other known superantigens based on phylogenetic analysis. The X-ray structure of SDM has been determined at 1.95 angstrom resolution. SDM shares the same characteristic fold with other superantigens, but it shows a major structural difference due to the lack of the alpha 5 helix between the beta 10 and beta 11 strands. A bound zinc ion was identified in the structure at the C-terminal domain of the molecule. SDM appears to bind to the major histocompatibility complex class II beta-chain through the zinc-binding site, as described by mutagenesis data and structural comparisons. T-cell binding instead shows a significant difference compared to other superantigens. The mutation of Asn11 (a conserved residue that is known to be significant for T-cell-receptor binding in other superantigens) and Lys15 to Ala did not cause any decrease in the mitogenic activity of SDM. This observation and the lack of the alpha 5 helix suggest alterations in T-cell-receptor binding. (C) 2007 Elsevier Ltd. All rights reserved.