Structural variability and concerted motions of the T cell receptor – CD3 complex
- Max Planck Institute of Colloids and Interfaces, Department of Theory and Bio-Systems, Germany
- Institute of Physics, Polish Academy of Sciences, Poland
Figures
Figure 1
Maps of residue-residue contacts (black disks) between the EC domains of the protein dimers TCRαβ, CD3εδ, and CD3εγ in the cryo-EM structure of the T cell receptor – CD3 complex (Dong et al., 2019).
Here, two residues are taken to be in contact if the minimum distance between non-hydrogen atoms of the residues is smaller than 0.45 nm. The loops and strands of the membrane-proximal constant …
Figure 2 with 1 supplement
Averaged maps of contacts between the EC domains of TCRαβ, CD3εδ, and CD3εγ in the MD simulation trajectories.
The shading of the contact disks indicates the contact probability, that is the fraction of simulation structures in which the contact is present. The contact analysis is based on 120 × 50 = 6000 …
Figure 2—figure supplement 1
Spearman correlation cofficients of the contact clusters in the contact maps of Figure 2.
The Spearman correlation coefficient assesses monotonic relations that can be linear or nonlinear and is calculated here for the numbers of contacts between non-hydrogen atoms of each cluster in the …
Figure 3 with 7 supplements
(a) and (b) MD conformations of the TCR – CD3 complex with different tilt angles of the TCRαβ ECdomain relative to the membrane normal.
The rotation angles of the TCRαβ ECdomain are 12.8° and 42.9° in the conformations (a) and (b), respectively. (c) Two-dimensional probability density function for the tilt angle and rotation angle …
Figure 3—figure supplement 1
Numbers of residue-residue contacts of TCR Cα and Cβ loops and strands in interaction with CD3s versus tilt angle of the TCRαβ EC domain.
Figure 3—figure supplement 2
Inclination angles of TM helices relative to the membrane normal as a function of the tilt angle of the TCRαβ ECdomain.
Figure 3—figure supplement 3
(a) Force-free tilt-angle distribution of the TCRαβ EC domain obtained from our simulations (blue data points) and tilt-angle distributions under transversal forces pN and 5 pN acting on the TCR-MHC complex, estimated from the force-free distribution; (b) local membrane thickness around the TM domain of the TCR – CD3 complex as a function of the tilt angle of the TCRαβ ECdomain.
The errors of the force-free tilt-angle distribution in (a) have been estimated as error of the mean of distributions obtained for 10 independent subsets of the MD conformations. The errors for the …
Figure 3—figure supplement 4
Tilt and rotation angle of the TCRαβ EC domain along the three exemplary trajectory segments shown in Figure 3—videos 1, 2 and 3.
Tilt and rotation angle of the TCRαβ EC domain along the three trajectory segments shown in Figure 3—videos 1, 2 and 3. Along these trajectory segments, the tilt angle increases from around 20° to …
Figure 3—video 1
Movie of trajectory segment 1.
Figure 3—video 2
Movie of trajectory segment 2.
Figure 3—video 3
Movie of trajectory segment 3.
Figure 4 with 1 supplement
Time-dependent trajectory averages for (a) the tilt angle and rotation angle of the TCRαβ EC domain, (b) the inclination angles of the TM helices of the eight protein chains relative to the membrane normal, (c) the number of contacts of structural elements in the TCR constant domains Cα and Cβ and of the variable domain Vα with the two CD3 EC domains.
Each data point is an average over the simulation structures of the 120 trajectories at the indicated time point, with error bars representing the error of the mean for these 120 structures. The …
Figure 4—figure supplement 1
Time-dependent trajectory averages for (a) the angle between the axes A and B of the TCRαβ EC domain and (b) minimal Cα-atom root-mean-square deviations (RSMDs) of the TCRαβ, CD3εγ, and CD3εδ EC domains as well as the transmembrane (TM) domain relative to the cryo-EM structure of the T cell receptor – CD3 complex (Dong et al., 2019).
Time-dependent trajectory averages for (a) the angle between the axes A and B of the TCRαβ EC domain and (b) minimal Cα-atom root-mean-square deviations (RSMDs) of the TCRαβ, CD3εγ, and CD3εδ EC …
