*2.3.1 Concept description*

Protein-fragment complementation refers to methods where a protein with reporter activity is split in two and fused to two proteins being tested for binding. Since the two halves do not interact with each other on their own, reporter activity is only recovered when the halves are fused to interacting proteins. The archetypal example of this approach is the yeast two-hybrid system (Y2H) which uses two halves of a transcriptional factor that can drive the expression of a report gene (**Figure 4**).
