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Insights into the structure of the LC13 TCR/HLA-B8-EBV peptide complex with molecular dynamics simulations

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Abstract

One key step in the immune response against infected or tumor cells is the recognition of the T-cell receptor (TCR) by class I major histocompatibility complexes. The complex between the HLA-B8 molecule and the immunodominant peptide with sequence FLRGRAYGL, derived from the Epstein-Barr virus, with the LC13 TCR has been determined by X-ray diffraction. The complex has been used as a starting point in a molecular dynamics study in order to investigate the dynamics of the complex association and to explore the specific interactions of the complex formation. The analyzed structures provided evidence that the peptide adopts an open type β-turn conformation close to C-terminal part, which dominates peptide/TCR interactions. Conformational energy landscape analysis indicated the presence of two conformational clusters in the peptide’s structure, underlying the backbone flexibility of the peptide despite being surrounded by two receptors. The peptide/MHC/TCR interface was found to hold significant number of solvent molecules, more specifically the peptide has been found to have approximately seventeen hydrogen bonds with water molecules. The molecular dynamics simulation indicated the disruption of some MHC/TCR contacts, mainly with the CDR1α loop. However, several other interactions emerged that resulted in a stable association during the 20 ns trajectory, as revealed by the buried surface area analysis.

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Acknowledgments

Parallel execution of NAMD was performed at the Research Center for Scientific Simulations (RCSS) of the University of Ioannina. The open source community (Linux, NAMD, GNU, etc.) is gratefully acknowledged for public release of all the necessary computer software needed for this research work.

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  1. Department of Economics, University of Ioannina, 451 10, Ioannina, Greece

    Athanassios Stavrakoudis

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Stavrakoudis, A. Insights into the structure of the LC13 TCR/HLA-B8-EBV peptide complex with molecular dynamics simulations. Cell Biochem Biophys 60, 283–295 (2011). https://doi.org/10.1007/s12013-011-9151-2

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