Zhen Ni, Yan Yue, Zhu Guangya, Zhu Tianxin, Zhang Qi, Chen Qi, Guo Yan, Zhu Jidong, Pan Qiuhui, Xie Jingjing
Department of Laboratory Medicine, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 200127, China.
Lingang Laboratory, Shanghai, 200031, China.
Nat Commun. 2025 Jul 17;16(1):6587. doi: 10.1038/s41467-025-61877-w.
Biomolecular condensates are membraneless compartments involved in a wide range of cellular processes. Despite their fundamental role in the spatiotemporal regulation of cellular functions, tools for precisely manipulating phase-separated condensates remain limited, and effective methods for discovering and functionalizing tunable phase separation modules from natural proteins are lacking. Here we present a rational engineering approach for androgen receptor (AR) and its clinically used drugs to create a chemical genetic platform, ARDrop, enabling condensates formation and dissolution. This platform is applied to a diverse set of proteins to achieve intended cellular functions, ensuring robust and long-lasting functionality through stable liquid-like properties. Our work develops a powerful toolkit for reversible manipulation of condensates that can be used for dissection of complicated cell signaling, laying the foundation for engineering designer condensates for synthetic biology applications.
生物分子凝聚物是参与多种细胞过程的无膜区室。尽管它们在细胞功能的时空调节中具有重要作用，但精确操纵相分离凝聚物的工具仍然有限，并且缺乏从天然蛋白质中发现和功能化可调节相分离模块的有效方法。在这里，我们提出了一种针对雄激素受体（AR）及其临床使用药物的合理工程方法，以创建一个化学遗传平台ARDrop，实现凝聚物的形成和溶解。该平台应用于多种蛋白质以实现预期的细胞功能，并通过稳定的类液体特性确保强大而持久的功能。我们的工作开发了一个用于可逆操纵凝聚物的强大工具包，可用于剖析复杂的细胞信号传导，为合成生物学应用设计定制凝聚物奠定基础。
