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Two common structural motifs for TCR recognition by staphylococcal enterotoxins

Rödström, Karin E J LU ; Regenthal, Paulina LU ; Bahl, Christopher; Ford, Alex; Baker, David and Lindkvist-Petersson, Karin LU (2016) In Scientific Reports 6.
Abstract

Superantigens are toxins produced by Staphylococcus aureus, called staphylococcal enterotoxins (abbreviated SEA to SEU). They can cross-link the T cell receptor (TCR) and major histocompatibility complex class II, triggering a massive T cell activation and hence disease. Due to high stability and toxicity, superantigens are potential agents of bioterrorism. Hence, antagonists may not only be useful in the treatment of disease but also serve as countermeasures to biological warfare. Of particular interest are inhibitors against SEA and SEB. SEA is the main cause of food poisoning, while SEB is a common toxin manufactured as a biological weapon. Here, we present the crystal structures of SEA in complex with TCR and SEE in complex with the... (More)

Superantigens are toxins produced by Staphylococcus aureus, called staphylococcal enterotoxins (abbreviated SEA to SEU). They can cross-link the T cell receptor (TCR) and major histocompatibility complex class II, triggering a massive T cell activation and hence disease. Due to high stability and toxicity, superantigens are potential agents of bioterrorism. Hence, antagonists may not only be useful in the treatment of disease but also serve as countermeasures to biological warfare. Of particular interest are inhibitors against SEA and SEB. SEA is the main cause of food poisoning, while SEB is a common toxin manufactured as a biological weapon. Here, we present the crystal structures of SEA in complex with TCR and SEE in complex with the same TCR, complemented with computational alanine-scanning mutagenesis of SEA, SEB, SEC3, SEE, and SEH. We have identified two common areas that contribute to the general TCR binding for these superantigens. This paves the way for design of single antagonists directed towards multiple toxins.

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author
organization
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type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
6
publisher
Nature Publishing Group
external identifiers
  • scopus:84975229866
  • wos:000375918000003
ISSN
2045-2322
DOI
10.1038/srep25796
language
English
LU publication?
yes
id
75a08a58-6940-4a71-bfb0-3f642e0a607d
date added to LUP
2017-01-30 11:39:12
date last changed
2017-09-18 11:34:46
@article{75a08a58-6940-4a71-bfb0-3f642e0a607d,
  abstract     = {<p>Superantigens are toxins produced by Staphylococcus aureus, called staphylococcal enterotoxins (abbreviated SEA to SEU). They can cross-link the T cell receptor (TCR) and major histocompatibility complex class II, triggering a massive T cell activation and hence disease. Due to high stability and toxicity, superantigens are potential agents of bioterrorism. Hence, antagonists may not only be useful in the treatment of disease but also serve as countermeasures to biological warfare. Of particular interest are inhibitors against SEA and SEB. SEA is the main cause of food poisoning, while SEB is a common toxin manufactured as a biological weapon. Here, we present the crystal structures of SEA in complex with TCR and SEE in complex with the same TCR, complemented with computational alanine-scanning mutagenesis of SEA, SEB, SEC3, SEE, and SEH. We have identified two common areas that contribute to the general TCR binding for these superantigens. This paves the way for design of single antagonists directed towards multiple toxins.</p>},
  author       = {Rödström, Karin E J and Regenthal, Paulina and Bahl, Christopher and Ford, Alex and Baker, David and Lindkvist-Petersson, Karin},
  issn         = {2045-2322},
  language     = {eng},
  month        = {05},
  publisher    = {Nature Publishing Group},
  series       = {Scientific Reports},
  title        = {Two common structural motifs for TCR recognition by staphylococcal enterotoxins},
  url          = {http://dx.doi.org/10.1038/srep25796},
  volume       = {6},
  year         = {2016},
}