通过重塑能源景观,重新调整诺奇ankyrin域的折叠路径
Katherine W Tripp1, Doug Barrick
1The T.C. Jenkins Department of Biophysics, Johns Hopkins University, 3400 North Charles Street, Baltimore, Maryland 21218, USA.
Journal of the American Chemical Society
|April 10, 2008
概括
通过添加稳定重复来设计像Notch ankyrin域这样的重复蛋白质,会改变它们的折叠机制. 这种蛋白质工程方法根据当地能量重新调整了折叠路径.
科学领域:
- 蛋白质工程是一种蛋白质工程.
- 生物物理学的生物物理.
- 结构生物学是结构生物学.
背景情况:
- 重复的蛋白质是模块化的,可以接受蛋白质的设计.
- 由共识设计的重复域表现出增强的热稳定性.
- 之前的研究表明,通过添加C端重复来重塑Notch ankyrin域的能量格局.
研究的目的:
- 研究能量格局的重塑如何影响重复蛋白质的折叠机制.
- 了解折叠通路对蛋白质结构修改的反应.
- 探索当地能源在选择折叠路径中的作用.
主要方法:
- 在每次重复中使用类似的替代保存的氨酸与甘氨酸.
- 分析工程Notch ankyrin域结构 (Nank1-5C1和Nank1-5C2) 的过渡状态集合.
- 比较野生型和工程结构的折叠动力学.
主要成果:
- 中央重复中的替换缓慢的野生类型的Notch ankyrin域折叠.
- 在C端子中的替换重复了工程Nank1-5C1和Nank1-5C2结构的缓慢折叠.
- 添加C端重复将过渡状态组合转移到C端,改变折叠路径.
结论:
- 工程重复蛋白质通过添加稳定性C端重复来重定向折叠路径.
- 诺奇基林域的折叠路径是根据当地的能量选择的.
- 这项研究提供了关于蛋白质结构,能量格局和折叠机制之间的关系的见解.
相关概念视频
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The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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