使用代谢学方法发现不和脂肪酸和核受体Nur77之间的蛋白质代谢物相互作用
Nawaporn Vinayavekhin1, Alan Saghatelian
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Journal of the American Chemical Society
|October 7, 2011
概括
研究人员发现不和脂肪酸 (UFA) 与孤儿核受体神经元衍生的克隆77 (Nur77) 结合. 这种约束改变了Nur7777的状态.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 代谢学 代谢学 代谢学
背景情况:
- 神经元衍生克隆77 (Nur77) 是一个孤儿核受体.
- 此前没有发现Nur77的天然配体.
研究的目的:
- 为了识别与Nur77.7结合的内源性脂质.
- 描述Nur77与已识别的脂质之间的相互作用.
主要方法:
- 利用一个代谢学平台来检测蛋白质代谢物相互作用 (PMIs).
- 采用生物物理和生物化学分析来描述连接物结合的特征.
主要成果:
- 发现Nur77联体结合域 (Nur77LBD) 丰富不和脂肪酸 (UFA).
- 确定了阿拉基酸和docosahexaenoic酸作为特定的UFA,它们与Nur77LBD结合.
- 证明UFA结合会诱导Nur77.7.中的形状和寡合变化.
结论:
- 不和脂肪酸是Nur77.7.第一个报告的内源性配体.
- 代谢学是一种强大的方法,用于发现新的蛋白质代谢物相互作用.
- 这些发现为Nur77调节和功能提供了新的见解.
相关概念视频
01:31Transducer Mechanism: Nuclear Receptors
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:45Regulation of Nuclear Protein Sorting
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
02:04Covalently Linked Protein Regulators
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These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.