How T cell receptors interact with peptide-MHCs: A multiple steered molecular dynamics study.

Détails

ID Serval
serval:BIB_7F6A1E44CD8E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
How T cell receptors interact with peptide-MHCs: A multiple steered molecular dynamics study.
Périodique
Proteins
Auteur(s)
Cuendet M.A., Zoete V., Michielin O.
ISSN
1097-0134 (Electronic)
ISSN-L
0887-3585
Statut éditorial
Publié
Date de publication
2011
Volume
79
Numéro
11
Pages
3007-3024
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: ppublish
Résumé
The T-cell receptor (TCR) interaction with antigenic peptides (p) presented by the major histocompatibility complex (MHC) molecule is a key determinant of immune response. In addition, TCR-pMHC interactions offer examples of features more generally pertaining to protein-protein recognition: subtle specificity and cross-reactivity. Despite their importance, molecular details determining the TCR-pMHC binding remain unsolved. However, molecular simulation provides the opportunity to investigate some of these aspects. In this study, we perform extensive equilibrium and steered molecular dynamics simulations to study the unbinding of three TCR-pMHC complexes. As a function of the dissociation reaction coordinate, we are able to obtain converged H-bond counts and energy decompositions at different levels of detail, ranging from the full proteins, to separate residues and water molecules, down to single atoms at the interface. Many observed features do not support a previously proposed two-step model for TCR recognition. Our results also provide keys to interpret experimental point-mutation results. We highlight the role of water both in terms of interface resolvation and of water molecules trapped in the bound complex. Importantly, we illustrate how two TCRs with similar reactivity and structures can have essentially different binding strategies. Proteins 2011; © 2011 Wiley-Liss, Inc.
Pubmed
Web of science
Création de la notice
25/10/2011 9:30
Dernière modification de la notice
20/08/2019 15:40
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