Multi-scale simulations of the T cell receptor reveal its lipid interactions, dynamics and the arrangement of its cytoplasmic region
Fig 6
Conformational changes within the TCR-CD3 during our simulations.
(A) Extracellular view of the TCR-CD3 TMR conformation from the cryo-EM structure (PDB:6JXR) compared to the TMR conformational change seen in the CGMD simulations. This conformational change was retained in the backmapped ATMD simulations throughout the 250 ns simulation time. (B) New interactions of the TCRα variable domain and of TCRβ constant domain with CD3δ (left), and of the TCRβ variable domain with CD3γ (right) seen in the backmapped ATMD simulations. (C) Snapshot from the end of one of our backmapped ATMD simulations of the entire TCR-CD3. The regions highlighted in boxes show pulled-in POPE headgroups whose amine (NH3) groups interact with the anionic sidechains of CD3 TMRs. The pulled-in POPE lipids are shown in cyan with their oxygen atoms shown in red and nitrogen atoms in blue. Hydrogen atoms are not shown for clarity. Anionic and cationic protein residues are represented as licorice sticks in red and blue, respectively. The TMR helices are shown as transparent cartoons. Water molecules are shown as transparent red spheres and the phosphorus atoms of all phospholipids are shown as black spheres defining the surface of the membrane. (D) Number of contacts of anionic residues of CD3 TMRs with nitrogen (N) atoms of POPC and POPE lipids from all backmapped ATMD simulations combined. (E) Extracellular view of the relative height of nitrogen atoms of all outer leaflet lipids (POPC, POPE, DPSM) mapped as a colour gradient from dark blue (low) to yellow (high). The TCR-CD3 TMR orientation is fixed in the center as shown in (A).