Discovery of a protein-metabolite interaction between unsaturated fatty acids and the nuclear receptor Nur77 using a metabolomics approach.
Discovery of a protein-metabolite interaction between unsaturated fatty acids and the nuclear receptor Nur77 using a metabolomics approach.
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DOI：
10.1021/ja208199h
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发表时间：
2011-11-02
影响因子：
15
通讯作者：
Saghatelian A
中科院分区：
文献类型：
--
作者：
Vinayavekhin N;Saghatelian A
神经元衍生的克隆77（Nur 77）是一种孤儿核受体，目前没有已知的天然配体。在这里，我们应用代谢组学平台来检测蛋白质-代谢物相互作用（PMI），以识别与Nur 77结合的脂质。使用这种方法，我们发现Nur 77配体结合结构域（Nur 77 LBD）可以从组织脂质混合物中富集不饱和脂肪酸（UFA）。Nur 77与花生四烯酸和二十二碳六烯酸之间的相互作用随后使用许多生物物理和生化测定进行了表征。总之，这些数据表明UFA与Nur 77 LBD结合，引起受体构象和寡聚化的变化。UFA是唯一的内源性脂质结合Nur 77，这突出了使用代谢组学在发现新的PMI。
Neuron-derived clone 77 (Nur77) is an orphan nuclear receptor with currently no known natural ligands. Here, we apply 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) could enrich unsaturated fatty acids (UFAs) from tissue lipid mixtures. The interaction between 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 Nur77, which highlights the use of metabolomics in the discovery of novel PMIs.