Functional Proteomics: Mapping Lipid-Protein Interactomes

Cell function is dependent upon the co-ordinated and dynamic formation of complex interaction networks between molecules of diverse biochemical properties. These networks, or interactomes, are comprised of macromolecular biopolymers; proteins, DNA, RNA and polysaccharides, in addition to non-polymer compounds such as small molecular metabolites. This myriad of interactions is highly regulated and any perturbation or alteration has potential to result in disease. Profiling protein-protein interactions has been the major focus of interactomics in the past few years Early efforts have included two-hybrid screens to identify binary binding interactions; more recent studies have used a range of mass spectrometry based methods to identify protein complexes that are a better reflection of multi-interactive nature of such complexes. Protein/small molecule interactions are equally important in modulating the function of their target proteins but few studies have analyzed these interactions on a large scale. The field is indeed still in its infancy due to difficulties in identifying metabolites but has recently benefitted from technological advances in mass spectrometry, data analysis software and metabolites database development for the measurement and identification of metabolites. The next step is to integrate metabolomic profiling to functional characterization of metabolic pathways by identifying systematically metabolite-protein interactions. Research efforts have in general been more focused on lipid-mediated interactions and this chapter reviews the global methods as well as their applications used to map lipid-protein interactomes based on mass spectrometry or arrays. The potential of these studies to deepen our understanding on the biological function of metabolites as protein effectors is also discussed.