生物活性蛋白开关的新设计
Robert A Langan1,2,3, Scott E Boyken1,2, Andrew H Ng4,5,6,7
1Department of Biochemistry, University of Washington, Seattle, WA, USA.
Nature
|July 26, 2019
概括
科学家通过控制相互竞争来重新设计可切换的蛋白质系统. 这些工程蛋白质和钥匙可以诱导蛋白质功能的控制,进步合成生物学.
科学领域:
- 蛋白质工程
- 合成生物学
- 生物化学
背景情况:
- 在生物学中,体调节至关重要,但在新的蛋白质设计中很难实现.
- 设计具有多个能量相似状态的蛋白质是一个重大挑战.
研究的目的:
- 探索可切换蛋白质系统的新设计.
- 通过相互竞争的分子间和分子内相互作用来调节蛋白质功能.
- 使用锁钥匙机制创建可诱导的蛋白质系统.
主要方法:
- 设计了一个静态的五螺旋蛋白,
- 设计了一种"锁"螺旋,可以通过分子内相互作用或被分子间"关键"所取代.
- 在锁螺旋上嵌入功能性图案 (结合,降解,核出口).
主要成果:
- 开发了直角钥匙系统,显示可切换的蛋白质功能.
- 在体外,酵母和哺乳动物细胞中验证的功能.
- 在钥匙引发的锁定时实现高达40倍的蛋白质功能激活.
结论:
- 通过诱导的形状变化控制可切换的蛋白质功能的成功设计.
- 建立了蛋白质设计的新范式,在合成生物学和细胞工程中具有潜在的应用.
- 开辟了创造复杂可控制生物系统的途径.
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