Membrane fusion, the process by which two distinct membranes combine to form a single bilayer, is central to many biological processes, including fertilization, neurotransmission and viral infection. Structural and functional studies in other labs have confirmed the salient features of this spring-loaded mechanism. We have also undertaken the development of pre-hairpin mimics that may elicit antibodies against HIV infection. However, peptides made from naturally occurring L-amino acid residues are generally poor leads for drug discovery, as they are rapidly degraded by proteases. For reasons of symmetry, the mirror images of these phage-displayed peptides interact with the target protein of the natural handedness.
Coiled coils are examples of such modules.
We continue to use coiled coils as model systems for studying protein folding and protein-protein interactions. The coiled coil is a structural motif consisting of a-helices that wrap around each other with a superhelical twist. Thus, there are many factors that determine the specificity of this seemingly simple protein motif. Towards this end, we utilize structural biology, computational biology, physical biochemistry and genetic screens. A key goal is to accurately predict protein structures at the detailed level of sidechain packing.