Protein-Mediated Induction of Membrane Curvature

The control of membrane curvature plays an important role in a number of membrane remodeling events. Recent evidence suggests that these processes are mediated by proteins which can sense or induce membrane curvature. Membrane curvature-inducing proteins can alter the shape of membranes and they typically have the ability to convert liposomes into small and highly curved vesicles or narrow membrane tubules. In order to understand the mechanism of membrane curvature induction, we have studied the membrane interaction of the N-BAR proteins (endophilin and amphiphysin) and EHD2. According to crystal structures, the N-BAR proteins have a bent helical structure with a curvature complementary to that of the highly curved membrane structures they induce. Using site-directed spin labeling and electron paramagnetic resonance, we found that this structure is maintained upon membrane interaction. The degree to which this structure interacts with the membrane, however, depends significantly upon the bilayer geometry and lipid composition. We also found that amphipathic helices are suspended on the convex side of the BAR domain and that these helices directly interact with the membrane where they are likely to promote membrane curvature by acting as molecular wedges. The ability of amphipathic helices to induce membrane curvature is further supported by our finding that α-synuclein, which can form an extended helical structure, readily cause tubulation and/or vesiculation under the appropriate lipid conditions. Structural and mechanistic studies describing how membrane interaction causes conformational changes in the aforementioned proteins and how these changes, in turn, affect membrane structure will be presented.