Department of Chemical and Systems Biology, Stanford University, Stanford, California 94305, USA.
J Am Chem Soc. 2012 Mar 7;134(9):3942-5. doi: 10.1021/ja209933r. Epub 2012 Feb 22.
Methods to rapidly and reversibly perturb the functions of specific proteins are desirable tools for studies of complex biological processes. We have demonstrated an experimental strategy to regulate the intracellular concentration of any protein of interest by using an engineered destabilizing protein domain and a cell-permeable small molecule. Destabilizing domains have general utility to confer instability to a wide range of proteins including integral transmembrane proteins. This study reports a destabilizing domain system based on the ligand binding domain of the estrogen receptor that can be regulated by one of two synthetic ligands, CMP8 or 4-hydroxytamoxifen.
快速且可逆地干扰特定蛋白质功能的方法是研究复杂生物过程的理想工具。我们已经证明了一种通过使用工程化的不稳定蛋白结构域和细胞通透的小分子来调节任何感兴趣的蛋白的细胞内浓度的实验策略。不稳定结构域具有广泛的用途,可以使包括整合跨膜蛋白在内的多种蛋白不稳定。本研究报告了一个基于雌激素受体配体结合域的不稳定结构域系统,该系统可以由两种合成配体 CMP8 或 4-羟基他莫昔芬来调节。