用AIEgen活性化学遗传探针绘制动态蛋白质聚类的映射
Chenxu Yan1, Wendi Zhu2, Runqi Li3
1Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Shanghai Key Laboratory of Functional Materials Chemistry, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, China.
Angewandte Chemie (International ed. in English)
|January 20, 2025
概括
一个新的化学遗传探测器跟踪活细胞中的蛋白质聚类动态. 这种工具可以超灵敏地监测内质网膜应激和药物查,推进细胞平衡研究.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 蛋白质聚类对细胞命运和稳态至关重要,但由于可逆行为和微环境变异,跟踪其动态具有挑战性.
- 现有的探针化学方法在检测蛋白质聚类及其相关微观环境中的微妙变化方面存在局限性.
- 了解蛋白质聚类动态对于破译细胞过程和疾病机制至关重要.
研究的目的:
- 开发一种新型的化学遗传探针,用于超灵敏地跟踪蛋白质聚类动态.
- 为了实时监测蛋白质聚类和分解,以应对细胞应激.
- 为了证明探针在揭示治疗诱导的内质网膜应激和促进药物查方面的实用性.
主要方法:
- 设计了一个双边量身定制的化学遗传探针,将两性聚合物诱导排放光原体 (AIEgen) QMSO3Cl与遗传化蛋白标签相结合.
- 探测器在黑暗状态下运行,直到它与感兴趣的蛋白质 (POI) 相互作用,确保低背景干扰.
- 探测器在蛋白质聚类时显示出显著的光"点亮" (67.5倍的增加),使其能够进行敏感的检测.
主要成果:
- 化学遗传探测器证明了监测蛋白质聚类动态的超高信号噪声比.
- 该探测器成功地追踪了活细胞中需要酶1 (IRE1) 的内醇在急性和慢性内质网膜 (ER) 应激下进行的聚类/分解.
- 该研究展示了探测器在3D环境中分析微度变化,集群动态和集群形态的能力.
结论:
- 开发的化学遗传探针提供了一个强大的工具,可以实时在活细胞内绘制动态蛋白质聚类的地图.
- 这种方法显著推进了细胞平衡,内质网膜应激和药物发现的研究.
- 探测器设计策略为未来分子和细胞动力学研究提供了一个有希望的途径.
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