结构可塑性作为Pro-Interleukin-18成熟的驱动因素
Jeffrey P Bonin1,2,3, James M Aramini1, Lewis E Kay1,2,3
1Departments of Molecular Genetics and Biochemistry, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Journal of the American Chemical Society
|October 24, 2024
概括
蛋白质的动态对于功能至关重要. 这项研究揭示了pro-interleukin-18 (pro-IL-18) 中的运动如何为酶结合和成熟做准备,揭示了具有特定链展开的塑性结构.
科学领域:
- 生物化学
- 结构生物学
- 分子动力学
背景情况:
- 生物分子动力学对于蛋白质的功能至关重要.
- 亲介素-18 (亲IL-18) 是一种亲炎性细胞因子前体.
- 卡斯帕酶-1和-4将亲IL-18切割成其成熟的活性形式.
研究的目的:
- 研究分子运动对亲IL-18成熟的作用.
- 了解蛋白质动力学如何促进酶结合.
主要方法:
- 用核磁共振 (NMR) 光谱来研究亲IL-18的动态.
- 探测器包括1H,13C和15N旋转探测器,跨越了广泛的时间尺度 (12次数).
- 使用交换测量来检测局部发生的事件.
主要成果:
- Pro-IL-18在β1和β*链中表现出具有毫秒时间尺度动态的塑性结构.
- 这些链表现出无酶和酶结合状态之间的显著结构差异.
- 隔离素48 (I48) 的侧链经历了埋入暴露的过渡,这表明局部解封.
- 交换证实了β1和β*链的局部展开.
结论:
- 一个动态事件层次为有效的酶结合提供了支持IL-18.
- 蛋白质的灵活性和局部展开是促成IL-18成熟的关键特征.
- 这些动态可能在调节促炎反应方面发挥关键作用.
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