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bioRxiv · 10.1101/219873

Peptide Terminus Tilting: an Unusual conformational transition of MHC Class I Revealed by Molecular Dynamics Simulations

Sun, Y.·Tian, P.
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Abstract

A conventional picture for major histocompatibility complex class I (MHCI) antigen presentation is that the terminal anchor residues of the antigenic peptide bind to the pockets at the bottom of the MHC cleft, leaving the central peptide residues exposed for T cell antigen receptor (TCR) recognition. However, in the present study, we show that in canonical or accelerated molecular dynamics (MD) simulations, the peptide terminus in some immunodominant peptide-MHCI (pMHCI) complexes can detach from their binding pockets and stretch outside the MHC cleft. These pMHCI complexes include the complex of the H-2Kb and the lymphocytic choriomeningitis virus (LCMV) gp33 peptide, and the complex of the HLA-A*0201 and the influenza A virus M1 peptide. The detached peptide terminus becomes the most prominent spot at the pMHC interface, and so can serves as a novel TCR recognition target. Thus, peptide terminus detaching may be a novel mechanism for MHC antigen presentation.

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Sun, Y., Tian, P.. 2017-11-15. Peptide Terminus Tilting: an Unusual conformational transition of MHC Class I Revealed by Molecular Dynamics Simulations. https://doi.org/10.1101/219873

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