J Am Chem Soc. 2019 Feb 27;141(8):3352-3355. doi: 10.1021/jacs.8b12382. Epub 2019 Feb 14.
Chemical methods that allow the spatial proximity of proteins to be temporally modulated are powerful tools for studying biology and engineering synthetic cellular behaviors. Here, we describe a new chemically controlled method for rapidly disrupting the interaction between two basally colocalized protein binding partners. Our chemically disrupted proximity (CDP) system is based on the interaction between the hepatitis C virus protease (HCVp) NS3a and a genetically encoded peptide inhibitor. Using clinically approved antiviral inhibitors as chemical disrupters of the NS3a/peptide interaction, we demonstrate that our CDP system can be used to confer temporal control over diverse intracellular processes. This NS3a-based CDP system represents a new modality for engineering chemical control over intracellular protein function that is complementary to currently available techniques.
化学方法可以使蛋白质的空间接近性在时间上得到调节，是研究生物学和工程合成细胞行为的有力工具。在这里，我们描述了一种新的化学控制方法，可以快速破坏两个基本共定位的蛋白质结合伴侣之间的相互作用。我们的化学破坏接近（CDP）系统基于丙型肝炎病毒蛋白酶（HCVp）NS3a 与一种遗传编码肽抑制剂之间的相互作用。我们使用临床批准的抗病毒抑制剂作为 NS3a/肽相互作用的化学破坏剂，证明我们的 CDP 系统可用于对不同的细胞内过程进行时间控制。基于 NS3a 的 CDP 系统代表了一种新的工程化方法，可对细胞内蛋白质功能进行化学控制，与目前可用的技术互补。
