Novel methods for studying multiprotein complexes in vivo

The current consensus is that the majority of proteins act in concert in the cell, as homo- and heteromeric complexes of two or more proteins that carry out discrete biological functions. A wide range of genomic, proteomic, biochemical, structural and biophotonic techniques have been employed over the years to study the protein-protein interactions that define complexes, with the end goal of producing a spatiotemporal map of these modular functional units throughout the cell. Recent advances in the analysis of in vivo complexes have greatly improved structural, functional and temporal resolution, and this review highlights novel approaches ranging from proximity-dependent labeling and cross-linking/mass spectrometry through pulse-chase epitope labeling and targeted protein degradation.