Quantitative Analysis of the Association Angle between T-cell Receptor Vα/Vβ Domains Reveals Important Features for Epitope Recognition
Fig 1
Cuboid and grid representations of the T–cell receptor geometries.
(A) Localisation of the considered Vα and Vβ variable domains within the ternary TCR:pMHC complex. A TCR consists of two chains, the α and the β chain (blue and red). Each chain is partitioned into two domains, the constant domain (Cα and Cβ shown transparently) and a variable domain (Vα and Vβ, here surrounded by cuboids). The Vα and Vβ domains form the binding interface to the major histocompatibility complex (MHC) molecule (green) presenting an antigenic peptide (magenta) to the TCR. This work focuses on the variable domains. (B) Superimposition of the TCR variable domains. (i) The TCR structures were superimposed on the Vα domains leading to displaced Vβ domains. (ii) Cuboids were placed around the superimposed Vα and Vβ domains. This unified description of the different domains allows a quantitative analysis of the displacement. (C) Preparation of the cuboid placement templates. Vα (blue) and Vβ (red) domains of the structure 2bnu are used as reference structure. Both chains are surrounded with cuboids of the size of their spatial extent. Residues considered for superimposition are determined in an iterative process (unused residues are depicted transparently). These residues are used to compute the angular displacement of the Vβ domain relative to the Vα domain. (D) Center of Rotation (CoR). (i) Different geometries of (only three for clearness) β-cuboid geometries (red), superimposed on the α-cuboids (blue). (ii) Grids were fit into the β-cuboids. (iii) For each grid point i, the sum of pairwise distances and the variance was computed according to Formula 2. (iv) The residues at the center of rotation (CoR, green sphere) were investigated. For most of the structures, a conserved pair hydrogen bond interaction between the α and the β chain is located directly at the CoR. These hydrogen bonds are established by conserved Q residues.