A comprehensive strategy for studying protein-metabolite interactions by metabolomics and native mass spectrometry

Abstract Protein-metabolite interactions play important roles in many cellular and physiological processes in biological systems. However, the lack of effective research approaches impedes the understanding of the protein-metabolite interactions. In this study, a novel comprehensive strategy by combining metabolomics platform with native mass spectrometry was developed for investigating the protein-metabolite interactions. Peroxisome proliferator-activated receptors gamma (PPARγ) is a lipid-binding nuclear receptors that plays a key role in regulating fatty-acid oxidation and lipid metabolism, which was selected as the model protein. Seven metabolites including lyso-phosphatidylcholine (LPC) 16:0, LPC18:0, LPC18:1, arachidonic acid, oleic acid, linoleic acid and palmitoleic acid (p