Context-Specific and Proximity-Dependent Labeling for the Proteomic Analysis of Spatiotemporally Defined Protein Complexes with Split-BioID

Proximity-dependent labeling techniques such as BioID and APEX2 allow the biotinylation of proteins proximal to a protein of interest in living cells. Following streptavidin pulldown and mass spectrometry analysis, this enables the identification of native protein-protein interactions. Here we describe split-BioID, a protein-fragment complementation assay that increases the resolution of BioID. Using this technique, context-specific protein complexes can be resolved.