Protein-protein interactions are the underpinnings of a vast number of cellular processes. In recent years, the convergence of biochemistry, cellular, and molecular biology has made available a number of powerful techniques for studying such interactions. These techniques vary in their sensitivity, efficiency, and rapidity, but judicial deployment of a combination of them has proved to be effective and reliable. Here, we highlight a version of the yeast two-hybrid assay originally pioneered by Fields and Song (1989) and subsequently enhancements by other investigators. We also briefly describe a number of new fluorescent imaging-based biophysical techniques for studying protein-protein interactions—FRET, FCS, and BiFC. Together, these constitute an impressive collection of tools for studying interactions among proteins.
