Work

Discovery of a Protein–Metabolite Interaction between Unsaturated Fatty Acids and the Nuclear Receptor Nur77 Using a Metabolomics Approach

Year: 2011

Type: article

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.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja208199h

Authors: Nawaporn Vinayavekhin, Alan Saghatelian

Institution: Harvard University

Language: English

Topic: Nuclear Receptors and Signaling

Subfield: Cellular and Molecular Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Institutes of Health