Figure 1.
Geometric definition of the TCR binding orientation and rigid displacement protocol.
(A) Rigid TCR translation along the x axis. (B) Rigid TCR rotation around the x axis. Rotation step is 5° in this study.
Table 1.
Statistics on TCR rotation profiles.
Figure 2.
TCR rotation profiles of the test set.
The polar contribution to the effective energy of the TCRpMHC complex is plotted against TCR rotation angle around the x axis, after an 8Å translation away from the pMHC. Positions that make steric clashes are ignored.
Figure 3.
Summary of the repartition of primary and secondary minima in TCR rotation profiles.
0° corresponds to the native orientation of each bound conformation. The positions of the primary minima are shown on the right half of the circle and reported on the right side histogram, which indicates the number of occurrences of each minimum in the test set. Secondary minima are similarly shown on the left half of the figure. The color code of histograms discriminates between global (blue) and non-global (red) minima. Outliers are not displayed.
Figure 4.
Landscape representation of the evolution of TCR polar energy rotation profiles of 1ao7 as a function of the TCR/pMHC distance.
The energetic preference for the native orientation (0°) is clearly visible. Rotation profiles were not computed at distances lower than 6Å due to the numerous steric clashes below that distance.
Figure 5.
Robustness and decomposition of the rotation profile.
(A) Comparison between the 1ao7 rotation profile (red) and the average of the 40 rotation profiles calculated after A6 TCR extracted from MD. Vertical bars are the standard deviations at each position. (B) Decomposition of the rotation profile of 1ao7. The polar effective energy is separated into contributions of the MHC (black), the CDR1,2 (red), the peptide (green) and the CDR3 (blue). (C) Average correlation coefficients of subgroups rotation profile regarding the rotation profile of the whole system. The CDR1,2 and MHC are responsible for 92% of the signal. The CDR3 and peptide are more important for discriminating the native from the opposite orientation.
Table 2.
Summary of correlation coefficients of the sub-systems CDR1,2, MHC, CDR3 and peptide, for each crystal structure.
Figure 6.
3D structure of the bound and the translated positions of the TCR for the three outlier complexes.
The incriminated residues are highlighted in ball and stick representation.
Figure 7.
Rigid pulling profiles of the test set.
The whole effective energy (see methods) is plotted against TCR translation away from the pMHC. Positions that make steric clashes are ignored.
Figure 8.
Starting position and rotation profiles of two unrelated proteins (lime green) in front of the pMHC.
(A) CD8 homodimer. (B) JAK2 tyrosine-protein kinase.
Figure 9.
Average rotation profile of 500 A6 TCR modeled by homology.
Vertical bars are the standard deviations at each position.