Proteome-wide mapping of cholesterol-interacting proteins in mammalian cells.
Proteome-wide mapping of cholesterol-interacting proteins in mammalian cells.
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DOI：
10.1038/nmeth.2368
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发表时间：
2013-03
期刊：
影响因子：
48
通讯作者：
Cravatt, Benjamin F.
中科院分区：
文献类型：
--
作者：
Hulce, Jonathan J.;Cognetta, Armand B.;Niphakis, Micah J.;Tully, Sarah E.;Cravatt, Benjamin F.
胆固醇是细胞膜的基本结构成分，是几种信号分子的前体。胆固醇发挥其作用，其自身在很大程度上是通过与蛋白质的特定相互作用来调节的。然而，存在于哺乳动物细胞中的固醇结合蛋白的全部补体仍是未知的。在这里，我们描述了一种化学蛋白质组学策略，该策略使用可点击的光反应性甾醇探针与定量质谱相结合，直接在活细胞中全局绘制胆固醇-蛋白质相互作用。我们确定了超过250种胆固醇结合蛋白，包括许多已建立的和以前未报道的与受体、通道和酶的相互作用。在新发现的相互作用中，突出的是调节糖、甘油脂和胆固醇本身的酶，以及那些参与囊泡运输和蛋白质糖基化和降解的酶，指出了可能将固醇浓度与其他代谢物和蛋白质定位和修饰的控制相结合的生化途径的关键节点。
Cholesterol is an essential structural component of cellular membranes and serves as a precursor for several classes of signaling molecules. Cholesterol exerts its effects and is, itself, regulated in large part by engaging in specific interactions with proteins. The full complement of sterol-binding proteins that exist in mammalian cells, however, remains unknown. Here, we describe a chemoproteomic strategy that uses clickable, photoreactive sterol probes in combination with quantitative mass spectrometry to globally map cholesterol-protein interactions directly in living cells. We identified over 250 cholesterol-binding proteins, including many established and previously unreported interactions with receptors, channels, and enzymes. Prominent among the newly identified interactions were enzymes that regulate sugars, glycerolipids, and cholesterol itself, as well as those involved in vesicular transport and protein glycosylation and degradation, pointing to key nodes in biochemical pathways that may couple sterol concentrations to the control of other metabolites and protein localization and modification.
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