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Introduction
A brief introduction expanding on the one already present in the article

Characteristics
Toxic Shock Syndrome Toxin (TSST-1), a prototype superantigen induced by a Staphylococcus aureus bacterium strain in susceptible hosts, acts on the vascular system by causing inflammation, fever, and shock. TSST-1 is a bacterial exotoxin that with a single polypeptide chain. The structure of TSST-1 is three-dimensional and consists of an alpha (α) and beta (β) domain. The two domains are adjacent from each other and possess unique qualities. Domain A is long alpha (α) helix surrounded by a 5-strand beta (β) sheet. Domain B is unique because it consists of (β) barrel made up of 5 β-strands. Crystallography methods show that the internal β-barrel of Domain B contains several hydrophobic amino acids and hydrophilic residues on the surface of the Domain, which allows TSST-1 to the cross mucous surfaces of epithelial cells. TSST-1 can be found in men, women, children, and even non-menstruating women. Staphylococcus aureus bacteria that produces the TSST-1's in any area of the body, live mostly in the vagina of infected women. One-third of all Toxic Shock Syndrome (TSS) cases however, are found in men. This statistic could possibly be due to surgical wounds or any skin wound

Production
TSST-1 is a protein encoded by the tstH gene, which is part of the mobile genetic element staphylococcal pathogenicity island 1. The toxin is produced in the greatest volumes during the post-exponential phase of growth, which is similar among pyrogenic toxin superantigens, also known as PTSAgs. Oxygen is required in order to produce TSST-1, in addition to the presence of animal protein, low levels of glucose, and temperatures between 37-40°C (98.6-104°F). Production is optimal at pH's close to neutral and when magnesium levels are low, and is further amplified by high concentrations of S. aureus, which indicates its importance in establishing infection.

TSST-1 differs from other PTSAgs in that its genetic sequence does not have a homolog with other superantigen sequences. TSST-1 does not have a cysteine loop, which is an important structure in other PTSAgs, and in fact it does not have any cysteine residues at all. Interestingly, the sequence for TSST-1 contains many hydrophobic amino acids, but the molecule itself is soluble in water. TSST-1 is also different from other PTSAgs in its ability to cross mucus membranes, which is why it is an important factor in menstrual TSS When the protein is translated, it is in a pro-protein form, and can only leave the cell once the signal sequence has been cleaved off. The explagr locus is one of the key sites of positive regulation for many of the S. aureus genes, including TSST-1. Additionally, alterations in the expression of the genes ssrB and srrAB have an impact on the transcription of TSST-1. Further, high levels of glucose inhibit transcription, since glucose acts as a catabolite repressor.

Mutations
Based on studies of various mutations of the protein it appears that the superantigenic and lethal portions of the protein are separate. One variant in particular, TSST-ovine or TSST-O, was important in determining the regions of biological importance in TSST-1. TSST-O does not cause TSS, and is non-mitogenic, and differs in sequence from TSST-1 in 14 nucleotides, which corresponds to 9 amino acids. Two of these are cleaved off as part of the signal sequence, and are therefore not important in the difference in function observed. From the studies observing the differences in these two proteins, it was discovered that residue 135 is critical in both lethality and mitogenicity, while mutations in residues 132 and 136 caused the protein to lose its ability to cause TSS, however there were still signs of superantigenicity. Interestingly, if the lysine at residue 132 in TSST-O is changed to a glutamate, the mutant regains little superantigenicity, but becomes lethal, meaning that the ability to cause TSS results from the glutamate at residue 132. The loss of activity from these mutations is not due to changes in the protein's conformation, but instead these residues appear to be critical in the interactions with T-cell receptors.

Purification
Samples of TSST-1 can be purified from bacterial cultures to use in in vitro testing environments, however this is not ideal due to the large number of factors that contribute to pathenogenesis in an in vivo environment. Additionally, culturing bacteria in vitro provides an environment which is rich in nutrients, in contrast to the reality of an in vivo environment, in which nutrients tend to be more scarce. TSST-1 can be purified by preparative isoelectric focusing for use in vitro or for animal models using a mini-osmotic pump.

Mechanism
The SAGs show remarkably conserved architecture and are divided into the N- and C- terminal domains. TSST-1 binds primarily to the alpha-chain of class II MHC exclusively through a low-affinity (or generic) binding site on the SAG N-terminal domain. This is opposed to other super antigens (SAGs) such as DEA and SEE, that bind to class II MHC through the low-affinity site, and to the beta-chain through a high-affinity site. This high-affinity site is a zinc-dependent site on the SAG C-terminal domain. When this site is bound, it extends over part of the binding groove, makes contacts with the bound peptide,and then binds regions of both the alpha and beta chains. MHC-binding by TSST-1 is partially peptide-dependent. Mutagenesis studies with SEA have indicated that both binding sites are required for optimal T-cell activation. These studies containing TSST-1 indicate that the TCR binding domain lies at the top of the back side of this toxin, though the complete interaction remains to be determined. A novel domain may exist in the SAGs that is separate from the TCR and class II MHC-binding domains. The domain consists of residues 150 to 161 in SEB, and similar regions exist in all the other SAGs as well. In this study a synthetic peptide containing this sequence was able to prevent SAG-induced lethality in D-galactosamine-sensitized mice with staphylcoccal TSST-1, as well as some other SAGs.