Extensive in vivo metabolite-protein interactions revealed by large-scale systematic analyses.
Extensive in vivo metabolite-protein interactions revealed by large-scale systematic analyses.
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DOI：
10.1016/j.cell.2010.09.048
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发表时间：
2010-11-12
期刊：
影响因子：
64.5
通讯作者：
Snyder M
中科院分区：
文献类型：
--
作者：
Li X;Gianoulis TA;Yip KY;Gerstein M;Snyder M
天然小化合物包含大多数细胞分子，并作为底物、产物、辅因子和配体结合蛋白质。然而，体内蛋白质-小代谢物相互作用的大规模研究尚未进行。我们开发了一种质谱分析方法，用于大规模鉴定酵母体内蛋白质-疏水小代谢物相互作用，并分析了结合麦角甾醇生物合成蛋白和蛋白激酶的化合物。许多这些蛋白质结合小代谢物；一些相互作用是已知的，但绝大多数是新的。重要的是，许多关键的调节蛋白，如蛋白激酶结合代谢物。麦角甾醇被发现与许多蛋白质结合，并可能作为一种一般调节剂起作用。它是哺乳动物AKT/SGK1激酶同源物Ypk1活性所必需的。我们的研究确定了脂质生物合成途径中潜在的关键调节步骤，并表明小代谢物可能在蛋白质活性和功能的调节中发挥比以前认识到的更普遍的作用。
Natural small compounds comprise most cellular molecules and bind proteins as substrates, products, cofactors and ligands. However, a large scale investigation of in vivo protein-small metabolite interactions has not been performed. We developed a mass spectrometry assay for the large scale identification of in vivo protein-hydrophobic small metabolite interactions in yeast and analyzed compounds that bind ergosterol biosynthetic proteins and protein kinases. Many of these proteins bind small metabolites; a few interactions were previously known, but the vast majority are novel. Importantly, many key regulatory proteins such as protein kinases bind metabolites. Ergosterol was found to bind many proteins and may function as a general regulator. It is required for the activity of Ypk1, a mammalian AKT/SGK1 kinase homolog. Our study defines potential key regulatory steps in lipid biosynthetic pathways and suggests small metabolites may play a more general role as regulators of protein activity and function than previously appreciated.
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