Extended Data Fig. 9: Analysis of MD simulations of GLMP-MFSD1apo and MFSD1apo.
From: MFSD1 with its accessory subunit GLMP functions as a general dipeptide uniporter in lysosomes
(a) Superposition of MFSD1 starting model (in blue, derived from the cryoEM model) and the structure after 500 ns of MD simulations of the three replicates (shades of red). (b) Superposition of GLMP-MFSD1 starting models (in blue, representing the cryoEM structure) and the complex after 500 ns of MD simulations of the three replicates (shades of grey). (c) RMSD (MFSD1 in relation to the starting CryoEM model) changes over the course of the MD simulation. The change in RMSD of MFSD1 in the apo form is shown in red, and the RMSD change of MFSD1 in the apo form as part of the complex with GLMP is given in grey blue. Each model was run in triplicates (Sim 1-3). (d) Conformational dynamics of the gate open to the lysosomal lumen (luminal gate) of MFSD1 in the absence/presence of the substrates and GLMP+MFSD1apo. The width of the opening of the luminal gate is defined as the distance between the centre of mass of two TM groups (group 1: TM1, TM2, and TM5; group 2: TM7, TM8, and TM11) and is plotted against its probability density. (e) A POPE lipid molecule (green) is only found between TMs of MFSD1 during simulations (run1-3) of the GLMP-MFSD1apo complex but not when simulations are run on MFSD1 only.
