Arp2/3复合物的分子机制激活由核化促进因子和一个actin单体的激活
Sahithya Sridharan Iyer1, Jiangbo Wu1, Thomas D Pollard2,3,4
1Department of Chemistry, Chicago Center for Theoretical Chemistry, Institute for Biophysical Dynamics, and James Franck Institute, The University of Chicago, Chicago, IL 60637.
概括
该Arp2/3复合体形成分支的活性纤维,对于细胞运动至关重要. 模拟揭示了一个能量屏障,以及N-WASp结合如何激活导线核化复合体.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 计算生物学 计算生物学
背景情况:
- Arp2/3 复合体对于核化分支性亚丁纤维是必不可少的.
- 动因动力学驱动关键的细胞过程,如运动和分裂.
- 了解Arp2/3复合体激活是细胞运动性研究的关键.
研究的目的:
- 阐明哺乳动物Arp2/3复合体激活的分子机制.
- 为了识别控制Arp2/3复杂的结构变化的能源景观.
- 调查核化促进因子在Arp2/3复合函数中的作用.
主要方法:
- 利用了元动力学和雨自由能源采样模拟.
- 进行了原子学分子动力学模拟.
- 模拟的哺乳动物Arp2/3复杂相互作用与N-WASp和动因单体.
主要成果:
- 鉴定了由于Arp2/Arp3 D-循环碰撞导致的不活跃和活跃Arp2/3复合状态之间的能量屏障 (20±6 kcal/mol).
- 证明神经维斯科特-阿尔德里希综合征蛋白 (N-WASp) 结合将该复合物转移到其活性构造.
- 显示的N-WASp结合暴露了Arp3上的一个actin单体结合位,稳定了过渡状态.
结论:
- 提出了一种物理接地途径,用于动丝分支的形成.
- 突出了蛋白质-蛋白质相互作用在调节Arp2/3复合体活性中的关键作用.
- 提供了分子洞察力,以启动actin聚合.
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