MS - BAR Domain Coupling

The ability of membrane proteins to induce curvature and budding in membranes is a critical component of vital cellular processes such as synaptic vesicle endocytosis. Recently, the ability of certain proteins to remodel membranes and induce membrane curvature has been shown to depend on highly conserved regions known as BAR domains. These domains are crescent-shaped dimers with positively charged residues on the concave surface which are believed to interact with phospholipid membranes. In the case of Drosophila amphiphysin, the BAR domain alone was sufficient to tubulate liposomes in vitro. In other cases, the BAR domain did not induce curvature but bound preferentially to liposomes with a higher curvature, thus demonstrating that certain BAR domains may have a curvature-sensing rather than a curvature-inducing function. This has been proposed as a novel mechanism for the spatial and temporal compartmentalization of proteins to certain membrane domains.

In this project, the multi-scale simulation methodology developed in this group will be used to study the curvature-sensing and curvature-inducing functions of Drosophila amphiphysin BAR domain interacting with a phospholipid bilayer.

In this phase of the project we will focus on the curvature-inducing function of BAR domains. This will include an analysis of how the N-terminal amphipathic helix, a motif found in other membrane deforming proteins, enhances this curvature-inducing function. Furthermore, the hypothesis that membrane bending is due solely to a net electrostatic attraction between the positively charged BAR surface and a negatively charged lipid bilayer will be tested. Finally, multi-scale strategies will be employed to study how locally modified membrane curvatures translate into global membrane curvature changes and remodeling.

At left:

A snapshot of the multi-scale coupled atomistic-level system (a) with the corresponding coarse-grained field theory EM2/BLOBs model (b). The atomistic-level system, in this case, is an M2 channel in a DMPC bilayer. The small square on the EM2 membrane is the "patch"; a region on the mesoscopic membrane that is designed to model the atomistic-lecel system of interest.

Research contiributed by Philip Bood
Image contributed by Gary Ayton