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在活细胞中遗传编码的生物对等的三腐烂

Yuchao Zhu¹, Wenlong Ding², Yulin Chen^2,3

¹New Cornerstone Science Laboratory, Synthetic and Functional Biomolecules Center, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Beijing National Laboratory for Molecular Sciences, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.

Nature chemistry

|February 28, 2024

概括

研究人员开发了一种新方法来控制蛋白质中的托 (Trp) 相互作用,使用一种基因编码的子托 (Trp-CAGE). 这允许精确操纵活细胞中的蛋白质功能,用于各种应用.

科学领域:

生物化学生物化学
分子生物学分子生物学
化学生物学化学生物学

背景情况:

(Trp) 由于其独特的化学特性,对蛋白质结构和功能至关重要.
在体内控制Trp相互作用是具有挑战性的,但对于蛋白质操纵至关重要.
现有的方法缺乏对Trp相互作用的概括性和特定位置的控制.

研究的目的:

开发一个可通用的平台来阻断和拯救蛋白质中的Trp相互作用.
为了使含有Trp的蛋白质能够在体内获得功能的操纵.
为了在活细胞中感兴趣的蛋白质上实现Trp的特定位点激活.

主要方法:

在基因上编码一个N1-乙烯基的Trp (Trp-CAGE).
利用一个优化的反向电子需求迪尔斯-阿尔德反应,以实现快速和生物对等的分解.
将Trp-CAGE策略应用于各种蛋白质家族,包括催化酶-过氧化酶和激酶.

主要成果:

在活细胞中证明了Trp-CAGE的快速和生物对等的衰变.
在不同的蛋白质家族中成功地激活Trp特定位点.
展示了对表观遗传信号调制的时间控制.
已经确定了超过28000个候选蛋白质用于生物对等的Trp激活.

结论:

Trp-CAGE策略提供了一个强大的工具,用于精确的,生物对等的Trp激活.
这种方法可以调节原生细胞环境中的蛋白质相互作用和功能.
该平台具有广泛的适用性,用于操纵各种蛋白质和理解细胞过程.

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