Membrane-binding mechanism of the EEA1 FYVE domain revealed by multi-scale molecular dynamics simulations
Fig 2
(A) Set-up of the CG simulation, with the truncated FYVE dimer (yellow) placed at a minimum distance of 10 nm from the lipid bilayer (blue; orange PI(3)P molecules) and rotated at random. (B) Minimum distance for each of the 15 repeats, showing repeats without binding (grey, 7/15), with canonical binding (similar to the binding mode of the crystal structure, orange, 6/15) and with non-canonical binding (blue, 2/15). (C) Two snapshots from one of the repeats with canonical binding, after 800 and 911 ns. The snapshots show the hinge-mechanism by which FYVE binds to the membrane. Sketches below for clarity. (D) Potential of mean force (PMF) calculations for the binding of FYVE to a lipid membrane containing PC and PI(3)P, in the canonical binding mode, showing mean (dark blue line), standard deviation (shaded area) as well as minimum and maximum values (dotted lines). The PMF well depth is 67 ± 2 kJ/mol.