Proteins and the macromolecular complexes they form are the effectors of cell biology. Studying cell biology therefore requires the ability to isolate distinct proteins along with other constituents of their associated macromolecules.
Affinity capture techniques have greatly facilitated the discovery, purification, and characterisation of endogenous protein complexes. These techniques leverage reagents able to target and capture proteins of interest assembled with physiological binding partners, from cell extracts. Although affinity capture has matured steadily as an approach, many technical shortcomings still limit its efficacy in the retrieval of intact, endogenous macromolecules. We address these challenges and develop mass spectrometry-based, affinity proteomic techniques for interactome mapping. We place special emphasis on approaches that also enable downstream structural and biochemical studies of purified macromolecules.