Targeting of proteins to membranes through hedgehog auto-processing
Targeting of proteins to membranes through hedgehog auto-processing
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DOI：
10.1038/nbt844
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发表时间：
2003-08-01
影响因子：
46.9
通讯作者：
Benson, JD
中科院分区：
文献类型：
--
作者：
Vincent, S;Thomas, A;Benson, JD
Hedgehog蛋白使用自动加工策略生成胆固醇偶联肽产物，在许多发育信号通路中充当细胞外配体。我们描述了一种利用刺猬自加工反应对异源蛋白进行细胞内修饰的方法，从而使其定位到细胞膜上。这种加工过程是自发发生的，没有辅助蛋白或其他酶的修饰。使用绿色荧光蛋白（GFP）和Hras的产物作为模型蛋白，我们展示了使用hedgehog基因自动处理来处理异源n端结构域，并将产生的生物活性产物引导到细胞膜上。该系统是一种将功能性肽和蛋白质靶向细胞膜的工具，也可能提供一种将肽或其他小分子定向到胆固醇代谢或调节成分的方法。
Hedgehog proteins use an auto-processing strategy to generate cholesterol- conjugated peptide products that act as extracellular ligands in a number of developmental signaling pathways. We describe an approach that takes advantage of the hedgehog auto-processing reaction to carry out intracellular modification of heterologous proteins, resulting in their localization to cell membranes. Such processing occurs spontaneously, without accessory proteins or modification by other enzymes. Using the green fluorescent protein (GFP) and the product of the Hras as model proteins, we demonstrate the use of hedgehog auto-processing to process heterologous N-terminal domains and direct the resulting biologically active products to cell membranes. This system represents a tool for targeting functional peptides and proteins to cell membranes, and may also offer a means of directing peptides or other small molecules to components of cholesterol metabolism or regulation.