Identification of Virus-Host Interactions.

No protein acts on its own to carry out its designated function. Proteins interact with other biomolecules to form complexes that perform a coordinated function. While proteins most often form complexes involving other proteins, they also interact with nucleic acids, lipids, carbohydrates, ions, and other small molecules and metabolites (Wang et al., Proteomics 22(15-16):e2100190, 2022; Veenstra, Proteomics 21:e2000235, 2021). While the early days of proteomics were focused on identifying and quantifying as many proteins as possible, scientists quickly recognized the power of proteomics to rapidly identify interactions between specific groups of proteins. All the necessary techniques have already been developed: methods to extract protein complexes (e.g., immunoaffinity purification under denaturing conditions), fractionate the complexes (e.g., chromatography and/or gel electrophoresis), identify the proteins that made up the complex (e.g., mass spectrometry (MS)), and validate the results (e.g., Western blotting, etc.). Indeed, one of the great accomplishments of the current proteomic era has been the speed at which protein complexes have been characterized (Labeau et al., Cell Rep 39:11074, 2022; May et al., Viruses 14:611, 2022; Havugimana et al., Nat Commun 13:4043, 2022), for example, as of 2022, the CORUM database (CORUM 3.1) contains data on 5134 mammalian protein complexes (Giurgiu et al., Nucleic Acids Res 47:D559-D563, 2019). The latest version of the Human Protein Complex Map (hu.MAP 2.0) contains information on over 7000 protein complexes (Drew et al., Mol Syst Biol 17:e10016, 2021). The IntAct Molecular Interaction Database contains over 700,000 binary molecular interactions curated from approximately 74,000 published experiments (Orchard et al., Nucleic Acids Res 42(Database issue):D358-D363, 2014). These databases show the amount of effort that continues to be expended in identifying biomolecular interactions, which demonstrates their importance in understanding how they affect cell function.