Protein Domain : Peptidase S1B, exfoliative toxin IPR008353

Type	Family
Description	This group of serine peptidases belong to MEROPS peptidase family S1, subfamily S1B (clan PA(S)). The type example is glutamyl endopeptidase I of Staphylococcus aureus, a well-characterised and specialised human pathogen expressing a variety of virulence factors to enable successful infection of the host. Symptoms usually manifest in cases of food poisoning, pyrogenic fever and toxic shock syndrome, and can prove lethal in immunocompromised victims. Of all the exotoxins secreted from the bacterial cell, superantigens and hemolysins are amongst the most studied [ ]. Of these, the former are well characterised, and several S. aureus super-antigenic enterotoxins exist that trigger excessive and aberrant T-cell activation in the host. Homologues of these S. aureus proteins have been found in Streptococcus pyogenes, and cause similar effects [ ]. In conventional Major Histocompatibility Complex (MHC)-II-restricted antigen processing, a peptide epitope is presented to a specific T-cell receptor (TCR) by the antigen presenting cell, and up to 0.0001% of the host T-cell repertoire is activated. By contrast, a bacterial superantigen (SAg) can bypass this process, binding non-specifically to constant regions on both the MHC-II and TCR. This results in up to 25% of the total host T-cell population being activated, with a massive release of inflammatory cytokines as a consequence. A recent study into the origins and functions of the S. aureus and S. pyogenessuperantigens has identified distinct protein domains that are responsible for the slightly different actions of each protein subgroup []. Based on these criteria, the staphylococcal and streptococcal entero-/exotoxins discovered so far can be placed into several groups/subfamilies. The EXFOL group contains those superantigens that cause exfoliative skin diseases in the human host, and shows some similarity to staphylococcalserine proteases [ ]. Although these proteins show no significant sequencesimilarity to the more "conventional"SAgs, they do function in the same way, binding both TCR and MHC-II molecules []. The EXFOL group of exotoxins also possess potent serine protease activity, and contain a functional domain found in other S. aureus serine proteases. To date, two distinct members of the subfamily have been characterised, both from S. aureus, and designated Exfoliative toxin A and B (Eta and Etb). The tertiary structure of Eta has been resolved to 1.7A using X-ray crystallography. This reveals that Eta contains unique "ETA-surface loops", no cysteine bridges, and a specific N-terminal helix that is crucial for substrate hydrolysis.
Short Name	Peptidase_S1B_tx