Studying the interactome with the yeast two-hybrid system and mass spectrometry

Protein interactions are crucial to the life of a cell. The analysis of such interactions is allowing biologists to determine the function of uncharacterized proteins and the genes that encode them. The yeast two-hybrid system has become one of the most popular and powerful tools to study protein-protein interactions. With the advent of proteomics, the two-hybrid system has found a niche in interactome mapping. However, it is clear that only by combining two-hybrid data with that from complementary approaches such as mass spectrometry (MS) can the interactome be analyzed in full. This review introduces the yeast two-hybrid system to those unfamiliar with the technique, and discusses how it can be used in combination with MS to unravel the network of protein interactions that occur in a cell.