Proteomic and interactomic insights into the molecular basis of cell functional diversity

The ability of living systems to adapt to changing conditions originates from their capacity to change their molecular constitution. This is achieved by multiple mechanisms that modulate the quantitative composition and the diversity of the molecular inventory. Molecular diversification is particularly pronounced on the proteome level, at which multiple proteoforms derived from the same gene can in turn combinatorially form different protein complexes, thus expanding the repertoire of functional modules in the cell. The study of molecular and modular diversity and their involvement in responses to changing conditions has only recently become possible through the development of new 'omics'-based screening technologies. This Review explores our current knowledge of the mechanisms regulating functional diversification along the axis of gene expression, with a focus on the proteome and interactome. We explore the interdependence between different molecular levels and how this contributes to functional diversity. Finally, we highlight several recent techniques for studying molecular diversity, with specific focus on mass spectrometry-based analysis of the proteome and its organization into functional modules, and examine future directions for this rapidly growing field.