A global protein–lipid interactome map

Mol Syst Biol. 6: 443Cellular processes are mediated by complex webs of interactions between macromolecules and metabolites, the complete set of which is often referred to as ‘interactome network’. Global and local properties of interactome networks appear to integrate genotypes into biological functions and phenotypes (Gavin et al , 2006). So far, empirical mapping efforts of cellular interactome networks have largely focused on interactions between macromolecules, such as protein–protein and DNA–protein interactions. Corresponding efforts to chart interactome networks between macromolecules and metabolites (sugars, nucleotides, amino acids or lipids) are still in their infancies. Lipids represent a large and diverse class of bioactive metabolites with mostly unknown molecular modes of action. Current knowledge about their ‘connectivity’ represents solitary islands on a vast open ocean rather than a comprehensive interconnected atlas.In an article just published in Molecular Systems Biology (Gallego et al , 2010), Gavin and colleagues describe a systematic screening strategy for protein–lipid interactions in Saccharomyces cerevisiae . Over 500 protein–lipid associations were catalogued, shedding light on the elusive modes of action of several bioactive lipids, and uncovering a novel dual‐binding specificity of a PH domain based on a novel structure. Additionally, a complete linkage analysis of protein–lipid‐binding fingerprints was modeled as predictors of protein localization (Figure 1).Figure 1. Yeast protein–lipid‐binding fingerprints as predictors of protein localization, domains and functions. ( A ) Yeast protein–lipid‐binding map summarizing protein–lipid‐binding frequencies, …