在酵母和哺乳动物中,SNARE蛋白Ykt6的不同形态动态
Jie Ji1, Yiping Yu1, Shaowen Wu2
1Department of Chemistry, Institute of Biomedical Sciences and Multiscale Research Institute of Complex Systems, Fudan University, Shanghai, China.
The Journal of biological chemistry
|June 28, 2023
概括
酵母Ykt6 (yYkt6) 呈现出比大鼠Ykt6 (rYkt6) 更开放的构造,影响其功能. 特定的突变揭示了控制Ykt6的关键相互作用.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- Ykt6是一种保存的SNARE蛋白质,对于细胞内膜贩运至关重要.
- 它的功能依赖于封闭和开放状态之间的形状过渡,由脂化和酸化调节.
- 在Ykt6定位和功能的特定物种差异表明潜在的结构变异.
研究的目的:
- 研究酵母Ykt6 (yYkt6) 和大鼠Ykt6 (rYkt6) 的结构功能关系和构造动态.
- 阐明对跨物种差异性Ykt6行为负责的分子机制.
主要方法:
- 生物化学表征 生物化学表征
- 单分子福斯特共振能量转移 (smFRET) 测量
- 分子动力学模拟的模拟.
主要成果:
- 与rYkt6.6相比,yYkt6显示了较高比例的开放形状.
- yYkt6不结合二甲基酸胆 (DPC),这是一个封闭状态rYkt6的抑制剂.
- 一个T46L/Q57A突变将yYkt6转移到一个封闭的,与DPC结合的状态,而Leu46则调解水相互作用.
- 酸化模拟 (S174D) 打开了rYkt6,而对应的突变 (S176D) 在yYkt6中稍微关闭了它.
结论:
- 形状的灵活性和特定的氨基酸残留物决定了Ykt6的独特功能状态和特定物种的活动.
- 这些发现提供了对不同生物体Ykt6功能的监管机制的洞察.
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