Protein engineering for selective proteomics

Post-translational modifications, complex formation, subcellular localization, and cell-type-specific expression create functionally distinct protein subpopulations that enable living systems to execute rapid and precise responses to changing conditions. Systems-level analysis of these subproteomes remains challenging, requiring preservation of spatial information or enrichment of species that are transient and present at low abundance. Engineered proteins have emerged as important tools for selective proteomics based on their capacity for highly specific molecular recognition and their genetic targetability. Here, we focus on new developments in protein engineering for selective proteomics of post-translational modifications, protein complexes, subcellular compartments, and cell types. We also address remaining challenges and future opportunities to integrate engineered protein tools across different subproteome scales to map the proteome with unprecedented depth and detail.