title: Discovery of a protein-metabolite interaction between unsaturated fatty acids and the nuclear receptor Nur77 using a metabolomics approach.
abstract: Neuron-derived clone 77 (Nur77) is an orphan nuclear receptor with currently no known natural ligands. Here we applied a metabolomics platform for detecting protein-metabolite interactions (PMIs) to identify lipids that bind to Nur77. Using this approach, we discovered that the Nur77 ligand-binding domain (Nur77LBD) enriches unsaturated fatty acids (UFAs) in tissue lipid mixtures. The interaction of Nur77 with arachidonic acid and docosahexaenoic acid was subsequently characterized using a number of biophysical and biochemical assays. Together these data indicate that UFAs bind to Nur77LBD to cause changes in the conformation and oligomerization of the receptor. UFAs are the only endogenous lipids reported to bind to Nur77, which highlights the use of metabolomics in the discovery of novel PMIs.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Nawaporn
authors.initials: N
authors.lastname: Vinayavekhin
authors.forename: Alan
authors.initials: A
authors.lastname: Saghatelian
mesh_terms: D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D055432:Metabolomics; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D005231:Fatty Acids, Unsaturated; C539821:NR4A1 protein, human; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid