Two-Hybrid Systems Studying a biological phenomenon? Which field? Well, it really doesn't matter. Whatever the area of interest, rest assured that protein-protein interactions are somehow, somewhere involved--if not directly, then as part of a structural or regulatory apparatus. Two-hybrid systems, pioneered by Fields and Song,1 are powerful systems for detecting interactions between and among macromolecules. The first systems described were for protein-protein interactions; later, the basic approach was modified and harnessed for the study of protein-DNA interactions, and more recently a three-hybrid system for studying RNA-protein interactions has been described.2
Utilizing techniques common to modern molecular biology laboratories, two-hybrid systems offer a number of advantages over other biochemical methods for detecting interactions between proteins, such as immunoprecipitation, biochemical copurification, and affinity chromatography. One significant advantage is that two-hybrid systems require neither purified proteins/antibodies nor prior knowledge of a protein's function. They offer the ultimate in flexibility: Pairs of...
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