可调节的,pH驱动的形状变化的新设计
Scott E Boyken1,2, Mark A Benhaim3, Florian Busch4
1Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
概括
在特定的酸度下改变形状. 这些新型蛋白质可以破坏细胞膜,显示可编程的蛋白质结构变化.
科学领域:
- 蛋白质工程
- 生物化学
- 分子生物学
背景情况:
- 蛋白质结构的变化对生物功能至关重要.
- 设计具有可切换形状的蛋白质是一个重大挑战.
- 之前的 de novo 蛋白质设计侧重于单个稳定状态.
研究的目的:
- 制定设计pH响应蛋白质结构开关的一般策略.
- 根据环境pH值来精确控制蛋白质结构的转变.
- 创建能够通过环境触发功能的新型蛋白质.
主要方法:
- 在埋藏的键网络中设计具有预先组织的胺残留的蛋白质结构.
- 创建具有受控的胺含量和疏水相互作用的同分类和异分类.
- 评估蛋白质稳定性,不同pH值的构造变化和膜破坏能力.
主要成果:
- 成功设计的稳定同分离体和异分离体,在pH值6.5以下经历大规模的构造变化.
- 通过调节胺网络和疏水相互作用来证明过渡pH和合作性的控制.
- 在实验室和体内观察到被设计的蛋白质在拆卸时破坏脂质膜.
结论:
- 通过 de novo 设计来编程环境触发的蛋白质构造变化已经建立了总体策略.
- 设计的基于histidine的网络可以精确控制pH响应蛋白质的行为.
- 这些工程蛋白显示出需要有针对性的膜破坏的应用的潜力.
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