Source:http://linkedlifedata.com/resource/pubmed/id/20944746
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
7317
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| pubmed:dateCreated |
2010-10-14
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| pubmed:databankReference | |
| pubmed:abstractText |
The pre-T-cell antigen receptor (pre-TCR), expressed by immature thymocytes, has a pivotal role in early T-cell development, including TCR ?-selection, survival and proliferation of CD4(-)CD8(-) double-negative thymocytes, and subsequent ?? T-cell lineage differentiation. Whereas ??TCR ligation by the peptide-loaded major histocompatibility complex initiates T-cell signalling, pre-TCR-induced signalling occurs by means of a ligand-independent dimerization event. The pre-TCR comprises an invariant ?-chain (pre-T?) that pairs with any TCR ?-chain (TCR?) following successful TCR ?-gene rearrangement. Here we provide the basis of pre-T?-TCR? assembly and pre-TCR dimerization. The pre-T? chain comprised a single immunoglobulin-like domain that is structurally distinct from the constant (C) domain of the TCR ?-chain; nevertheless, the mode of association between pre-T? and TCR? mirrored that mediated by the C?-C? domains of the ??TCR. The pre-TCR had a propensity to dimerize in solution, and the molecular envelope of the pre-TCR dimer correlated well with the observed head-to-tail pre-TCR dimer. This mode of pre-TCR dimerization enabled the pre-T? domain to interact with the variable (V) ? domain through residues that are highly conserved across the V? and joining (J) ? gene families, thus mimicking the interactions at the core of the ??TCR's V?-V? interface. Disruption of this pre-T?-V? dimer interface abrogated pre-TCR dimerization in solution and impaired pre-TCR expression on the cell surface. Accordingly, we provide a mechanism of pre-TCR self-association that allows the pre-T? chain to simultaneously 'sample' the correct folding of both the V and C domains of any TCR ?-chain, regardless of its ultimate specificity, which represents a critical checkpoint in T-cell development. This unusual dual-chaperone-like sensing function of pre-T? represents a unique mechanism in nature whereby developmental quality control regulates the expression and signalling of an integral membrane receptor complex.
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| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
|
| pubmed:issn |
1476-4687
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| pubmed:author |
pubmed-author:BeddoeTravisT,
pubmed-author:BerryRichardR,
pubmed-author:ChenZhenjunZ,
pubmed-author:ChewSock HuiSH,
pubmed-author:CowiesonNathan PNP,
pubmed-author:GodfreyDale IDI,
pubmed-author:KingGlenn FGF,
pubmed-author:Kjer-NielsenLarsL,
pubmed-author:La GrutaNicole LNL,
pubmed-author:McCluskeyJamesJ,
pubmed-author:PangSiew SiewSS,
pubmed-author:PeruginiMatthew AMA,
pubmed-author:PurcellAnthony WAW,
pubmed-author:RossjohnJamieJ,
pubmed-author:TiganisTonyT,
pubmed-author:WangChristinaC,
pubmed-author:WilceMatthew C JMC,
pubmed-author:WilliamsNeal KNK
|
| pubmed:issnType |
Electronic
|
| pubmed:day |
14
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| pubmed:volume |
467
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
844-8
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| pubmed:meshHeading |
pubmed-meshheading:20944746-Crystallography, X-Ray,
pubmed-meshheading:20944746-Gene Rearrangement, T-Lymphocyte,
pubmed-meshheading:20944746-Humans,
pubmed-meshheading:20944746-Models, Molecular,
pubmed-meshheading:20944746-Mutation,
pubmed-meshheading:20944746-Protein Folding,
pubmed-meshheading:20944746-Protein Multimerization,
pubmed-meshheading:20944746-Protein Structure, Tertiary,
pubmed-meshheading:20944746-Receptors, Antigen, T-Cell,
pubmed-meshheading:20944746-Receptors, Antigen, T-Cell, alpha-beta,
pubmed-meshheading:20944746-Signal Transduction,
pubmed-meshheading:20944746-Solutions,
pubmed-meshheading:20944746-T-Lymphocytes
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| pubmed:year |
2010
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| pubmed:articleTitle |
The structural basis for autonomous dimerization of the pre-T-cell antigen receptor.
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| pubmed:affiliation |
The Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|