The two main strategies for experimental interactome mapping. In yeast two-hybrid (Y2H) screening, physical interaction between two hybrid proteins within the nucleus of a yeast cell reconstitutes a transcription factor that activates expression of a selectable reporter gene. Y2H returns binary interactions. In affinity purification followed by mass spectrometry (AP–MS), a protein complex between a tagged bait protein and associated cellular proteins is purified by affinity purification, and the constituents of the complex are identified by mass spectrometry. AP–MS returns co-complex
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