Computer Simulation of Membrane Tubulation by EFC F-BAR Domain Lattices

Cells are dynamically sculpted into many types of compartments by cellular membranes, in some cases with the help of BAR domain proteins. BAR domain proteins act under in vitro conditions are found to induce formation of tubules. We have seen in coarse-grained molecular dynamics simulation stretching over 100 microseconds how a flat membrane is curved into a tube when F-BAR domain proteins are arranged on the membrane surface as a regular lattice of parallel rows. The simulations could also characterize the membrane bending properties of F-BAR domains in different lattice arrangements, showing membrane curvatures with radii ranging from 25 to 100 nm.Lastly, the simulations reveal two key structural features of F-BAR domain that facilitate efficient binding to membranes and membrane curving: (1) Curving is promoted by close contact between phosphoserine lipid head groups and clusters of cationic residues along the membrane facing surface of F-BAR domains, namely lysine and arginine residues 30, 33, 110, 113, 114, and 139, 140, 146, 150, respectively. (2) Within the 100 ns of contact, the F-BAR domain hinge region, through a 20 degree rotation of the helix moment of inertia, establishes a close contact between protein and membrane. (1) and (2) result in membrane bending on a microsecond-to-millisecond time scale.