Membrane proteins play crucial roles in many biological processes. Yet, for such an important family of proteins, little is known about their structural properties. If we are to understand the forces which determine folding and assembly leading to proper function of membrane proteins, it is essential to be able to perform experiments on a model system whose structure is known and the effects of mutagenesis can be easily assessed. Of the membrane proteins of known structure, none possess properties which make for an ideal model system: they are either too big making it difficult to assess the effects of mutagenesis or there exist few if any assays to determine proper folding and function of the protein and its mutants. I propose to convert a soluble protein of known structure, the leucine zipper region of GCN4, into a transmembrane protein. Rather than applying a rational de novo design, a genetic approach will be used to select out possible candidate peptides from a pool of sequences. While I hope to learn much from the process of designing such a protein, the eventual goal will be to utilize the converted protein as a model system to study properties of membrane proteins. Ultimately, I hope what is learned from these studies will lead to solving more three dimensional structures of membrane proteins.
