T cell receptor-ligand interactions: a conformational preequilibrium or an induced fit.

Détails

ID Serval
serval:BIB_E61AA2828AB8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
T cell receptor-ligand interactions: a conformational preequilibrium or an induced fit.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Gakamsky D.M., Luescher I.F., Pecht I.
ISSN
0027-8424
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
101
Numéro
24
Pages
9063-9066
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Kinetic parameters of T cell receptor (TCR) interactions with its ligand have been proposed to control T cell activation. Analysis of kinetic data obtained has so far produced conflicting insights; here, we offer a consideration of this problem. As a model system, association and dissociation of a soluble TCR (sT1) and its specific ligand, an azidobenzoic acid derivative of the peptide SYIPSAEK-(ABA)I (residues 252-260 from Plasmodium berghei circumsporozoite protein), bound to class I MHC H-2K(d)-encoded molecule (MHCp) were studied by surface plasmon resonance. The association time courses exhibited biphasic patterns. The fast and dominant phase was assigned to ligand association with the major fraction of TCR molecules, whereas the slow component was attributed to the presence of traces of TCR dimers. The association rate constant derived for the fast phase, assuming a reversible, single-step reaction mechanism, was relatively slow and markedly temperature-dependent, decreasing from 7.0 x 10(3) at 25 degrees C to 1.8 x 10(2) M(-1).s(-1) at 4 degrees C. Hence, it is suggested that these observed slow rate constants are the result of unresolved elementary steps of the process. Indeed, our analysis of the kinetic data shows that the time courses of TCR-MHCp interaction fit well to two different, yet closely related mechanisms, where an induced fit or a preequilibrium of two unbound TCR conformers are operational. These mechanisms may provide a rationale for the reported conformational flexibility of the TCR and its unusual ligand recognition properties, which combine high specificity with considerable crossreactivity.
Mots-clé
Amino Acid Sequence, Animals, H-2 Antigens/chemistry, H-2 Antigens/metabolism, Kinetics, Ligands, Models, Molecular, Peptides/chemistry, Peptides/metabolism, Plasmodium berghei/chemistry, Plasmodium berghei/genetics, Protein Conformation, Protozoan Proteins/chemistry, Protozoan Proteins/genetics, Receptors, Antigen, T-Cell/chemistry, Receptors, Antigen, T-Cell/genetics, Recombinant Proteins/chemistry, Recombinant Proteins/genetics, Surface Plasmon Resonance
Pubmed
Web of science
Open Access
Oui
Création de la notice
28/01/2008 11:19
Dernière modification de la notice
20/08/2019 16:09
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