Geometry Dynamics of α -Helices in Different Class I Major Histocompatibility Complexes.

Reiner Ribarics,Wolfgang Schreiner,Michael Kenn,Rudolf Karch,Nevena Ilieva

doi:10.1155/2015/173593

Abstract

MHC α-helices form the antigen-binding cleft and are of particular interest for immunological reactions. To monitor these helices in molecular dynamics simulations, we applied a parsimonious fragment-fitting method to trace the axes of the α-helices. Each resulting axis was fitted by polynomials in a least-squares sense and the curvature integral was computed. To find the appropriate polynomial degree, the method was tested on two artificially modelled helices, one performing a bending movement and another a hinge movement. We found that second-order polynomials retrieve predefined parameters of helical motion with minimal relative error. From MD simulations we selected those parts of α-helices that were stable and also close to the TCR/MHC interface. We monitored the curvature integral, generated a ruled surface between the two MHC α-helices, and computed interhelical area and surface torsion, as they changed over time. We found that MHC α-helices undergo rapid but small changes in conformation. The curvature integral of helices proved to be a sensitive measure, which was closely related to changes in shape over time as confirmed by RMSD analysis. We speculate that small changes in the conformation of individual MHC α-helices are part of the intrinsic dynamics induced by engagement with the TCR.

Highlights

T cells play a major role in both innate immunity and adaptive immunity
We speculate that small changes in the conformation of individual major histocompatibility complexes (MHC) α-helices are part of the intrinsic dynamics induced by engagement with the T cell receptors (TCRs)
We applied the quantification method to three large TCR/pMHC complexes, due to their size being accessible by molecular dynamics (MD) simulation studies only since recently

Summary

Introduction

T cells play a major role in both innate immunity and adaptive immunity. Their surface-bound T cell receptors (TCRs) recognise antigens and thereby detect hazardous organisms or changes inside cells. TCRs recognize short peptide fragments (p) that are bound to major histocompatibility complexes (MHC). MHCs are surface-bound proteins and their role is to present peptide fragments to TCRs, be they self- or alloantigens. MHCs have a cleft that is able to bind peptide fragments. This cleft comprises two α-helices and five subjacent lateral β-strands forming a sheet or floor of the cleft.

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