Linked Life Data

17303163

Source:http://linkedlifedata.com/resource/pubmed/id/17303163

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-19
pubmed:databankReference
pubmed:abstractText
Superantigens (SAgs) are potent microbial toxins that bind simultaneously to T cell receptors (TCRs) and class II major histocompatibility complex molecules, resulting in the activation and expansion of large T cell subsets and the onset of numerous human diseases. Within the bacterial SAg family, streptococcal pyrogenic exotoxin I (SpeI) has been classified as belonging to the group V SAg subclass, which are characterized by a unique, relatively conserved approximately 15 amino acid extension (amino acid residues 154 to 170 in SpeI; herein referred to as the alpha3-beta8 loop), absent in SAg groups I through IV. Here, we report the crystal structure of SpeI at 1.56 A resolution. Although the alpha3-beta8 loop in SpeI is several residues shorter than that of another group V SAg, staphylococcal enterotoxin serotype I, the C-terminal portions of these loops, which are located adjacent to the putative TCR binding site, are structurally similar. Mutagenesis and subsequent functional analysis of SpeI indicates that TCR beta-chains are likely engaged in a similar general orientation as other characterized SAgs. We show, however, that the alpha3-beta8 loop length, and the presence of key glycine residues, are necessary for optimal activation of T cells. Based on Vbeta-skewing analysis of human T cells activated with SpeI and structural models, we propose that the alpha3-beta8 loop is positioned to form productive intermolecular contacts with the TCR beta-chain, likely in framework region 3, and that these contacts are required for optimal TCR recognition by SpeI, and likely all other group V SAgs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-2836
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
367
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
925-34
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Crystal structure of the streptococcal superantigen SpeI and functional role of a novel loop domain in T cell activation by group V superantigens.
pubmed:affiliation
Department of Microbiology and Immunology, The University of Western Ontario, London, ON, Canada N6A 5B8.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural