Nonetheless, the molecular basis for specificity in these interactions remains incompletely understood. My lab is interested in understanding the factors leading to specificity in coiled-coil interactions. Coiled-coil domains are found in a wide variety of proteins of biological and medicinal interest. For example, many transcription factors contain coiled coils, including GCN4, the Serum Response Factor, and the human oncogenes Jun, Fos, and Myc. In addition to their biological and medicinal importance, coiled coils provide a useful model system for the study of specific protein-protein interactions.
Coiled coils consist of two or more alpha-helices interacting to form a supercoil.
Because of regular features in the primary amino acid sequences of coiled coils, it has been possible to generate computer algorithms that can identify coiled-coil domains with a high degree of accuracy. Thus, to fully understand the function of a newly identified coiled coil forming segment, we must also be able to specify potential partner strands and predict its oligomerization state and helix orientation. My lab is working to understand the interactions that lead to helix orientation and partner preference in sufficient detail that we can predict the function of a coiled-coil protein from its sequence. We are using sequence-specific DNA binding as a probe for helix orientation preference and for partner specificity in coiled coils. This strategy allows us to generate and quantitatively test large numbers of mutant coiled coils efficiently and permits us to take advantage of in vivo selection techniques.