不连续的双域蛋白质的折叠路径
Ganesh Agam1,2,3, Anders Barth1,2,4, Don C Lamb5,6
1Department of Chemistry, Ludwig-Maximilians University Munich, Munich, Germany.
Nature communications
|January 23, 2024
概括
这项研究揭示了多域蛋白质如何折叠,重点关注一种双变异型马尔托结合蛋白 (DM-MBP). 研究结果表明,动态中间体是克服折叠障碍的关键,即使有陪伴者协助.
科学领域:
- 生物化学和分子生物学
- 蛋白质折叠的动力学
- 结构生物学 结构生物学
背景情况:
- 高级生物中的大多数蛋白质都是多域的,但体外折叠研究往往侧重于更简单的单域蛋白质.
- 了解不连续的多域蛋白质的折叠机制对于理解复杂的生物过程至关重要.
研究的目的:
- 研究一种缓慢折叠的马尔托结合蛋白 (DM-MBP) 双突变体的展开和重新折叠路径,作为不连续的两域蛋白的模型.
- 阐明折叠中间体和伴侣系统在多域蛋白的相互依赖折叠中的作用.
主要方法:
- 使用单分子弗斯特共振能量转移 (FRET) 实验,采用两种和三种颜色的设置.
- 分析了DM-MBP的展开/重新折叠动力学和形状动态,包括它与GroEL/ES护送系统的相互作用.
主要成果:
- 确定了一个动态折叠的中间群体,涉及N端域 (NTD),C端域 (CTD) 和域接口.
- 观察到展开和紧状态之间的中间体的快速波动,紧状态类似于折叠的形状.
- 确定NTD的延迟折叠受到热屏障的控制,随后是动态CTD的折叠.
结论:
- DM-MBP的折叠通过一个动态中间体进行,突出显示了不连续的多域蛋白折叠所需的相互依赖性和微妙调整.
- 沙佩罗宁GroEL/ES通过将其导入相同的动态中间体来加速DM-MBP折叠,有效地减少了克服热屏障的构造空间.
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