Modeling of the TCR-MHC-peptide complex.

Details

Serval ID
serval:BIB_6F4A32D7C592
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Modeling of the TCR-MHC-peptide complex.
Journal
Journal of molecular biology
Author(s)
Michielin O., Luescher I., Karplus M.
ISSN
0022-2836
Publication state
Published
Issued date
2000
Peer-reviewed
Oui
Volume
300
Number
5
Pages
1205-1235
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Abstract
The methodology for generating a homology model of the T1 TCR-PbCS-K(d) class I major histocompatibility complex (MHC) class I complex is presented. The resulting model provides a qualitative explanation of the effect of over 50 different mutations in the region of the complementarity determining region (CDR) loops of the T cell receptor (TCR), the peptide and the MHC's alpha(1)/alpha(2) helices. The peptide is modified by an azido benzoic acid photoreactive group, which is part of the epitope recognized by the TCR. The construction of the model makes use of closely related homologs (the A6 TCR-Tax-HLA A2 complex, the 2C TCR, the 14.3.d TCR Vbeta chain, the 1934.4 TCR Valpha chain, and the H-2 K(b)-ovalbumine peptide), ab initio sampling of CDR loops conformations and experimental data to select from the set of possibilities. The model shows a complex arrangement of the CDR3alpha, CDR1beta, CDR2beta and CDR3beta loops that leads to the highly specific recognition of the photoreactive group. The protocol can be applied systematically to a series of related sequences, permitting the analysis at the structural level of the large TCR repertoire specific for a given peptide-MHC complex.
Keywords
Algorithms, Amino Acid Sequence, Amino Acid Substitution/genetics, Binding Sites, Computer Simulation, Epitopes, T-Lymphocyte/chemistry, Epitopes, T-Lymphocyte/immunology, Histocompatibility Antigens Class I/chemistry, Histocompatibility Antigens Class I/immunology, Humans, Hydrogen Bonding, Models, Molecular, Molecular Sequence Data, Mutation/genetics, Peptide Fragments/chemistry, Peptide Fragments/immunology, Protein Conformation, Receptors, Antigen, T-Cell/chemistry, Receptors, Antigen, T-Cell/genetics, Reproducibility of Results, Sequence Alignment, Software, Static Electricity, Substrate Specificity, Thermodynamics
Pubmed
Web of science
Create date
28/01/2008 11:20
Last modification date
20/08/2019 14:28
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