Extended Data Fig. 7: MD simulations reveal TPC membrane interactions.
a) Selected snapshots of MD simulation time series showing TPC interaction with the membrane. The minimum distance between TWD40-1, TWD40-2 and TASH3 and the membrane was calculated to monitor TPC-membrane interaction. The last 2 μs of trajectories in which TWD40-1, TWD40-2 and TASH3 simultaneously bind the membrane, were selected for follow up analyses. Phosphatidylcholine is depicted in black, phosphatidylethanolamine is depicted in dark grey, PS, PA, PI4P and PI4,5P2 are depicted in shades of blue. b) ZZ component of the rotational matrix visualizing rotation of the TPC in the simulation box in time. 4 out 5 simulation replicas show no rotation of the complex once bound to the membrane. Rzz = 1 no rotation, Rzz = 0 rotation 90°/270°, Rzz = -1 rotation 180°. c) Residues of the membrane-binding interface of the TPC hexamer interacting with phosphatidylserine (PS). d) PI4P, PI4,5P2, PA and PS densities around TPC hexamer. PI4P, PI4,5P2 cluster at the membrane-binding interface. e) Membrane curvature over the last 2 μs calculated for each MD trajectory. In 3 out of 5 simulation repeats, TPC interacting with the membrane induces the concave membrane curvature. The time indications represent computational time of CG-MD simulations, which cannot be easily compared to the actual endocytic life times observed in microscopy experiments.
