宏分子拥挤对抗CRISPR AcrIIC3/NmeCas9复合体的影响:来自缩放粒子理论,分子动力学和弹性网络模型的见解
Ariana Delgado1, Joan Vera-Villalobos2, José Luis Paz3
1Instituto Venezolano de Investigaciones Científicas (IVIC), Centro de Biomedicina Molecular (CBM), Laboratorio de Química Biofísica Teórica y Experimental (LQBTE), 4001 Maracaibo, Zulia, Venezuela; Universidad del Zulia (LUZ), Facultad Experimental de Ciencias (FEC), Departamento de Química, Laboratorio de Química Teórica y Computacional (LQTC), 4001 Maracaibo, Venezuela.
International journal of biological macromolecules
|May 31, 2023
概括
大分子拥挤稳定了Neisseria meningitidis Cas9 (NmeCas9) 和其抑制剂AcrIIC3复合体的形成. 较小的拥挤和较弱的吸引力相互作用增强了这种稳定性,有利于紧的二元结构.
科学领域:
- 生物化学 生化学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 脑膜炎Neisseria的Cas9 (NmeCas9) 蛋白被AcrIIC3.3.所抑制.
- 了解NmeCas9和AcrIIC3之间复杂的形成对于其机制性见解至关重要.
研究的目的:
- 调查宏分子拥挤对 (NmeCas9/AcrIIC3) 2同位体的形成和稳定性的影响.
- 探索群体大小和蛋白质群体相互作用对二聚体稳定性的影响.
主要方法:
- 利用基于尺度粒子理论 (SPT) 的统计热力学模型.
- 嵌入有吸引力和排斥力的蛋白质-crowder贡献.
- 使用PEG作为拥挤剂的动态,弹性网络和统计潜力模型.
主要成果:
- 大分子拥挤显著稳定了 (NmeCas9/AcrIIC3) 2二次体的形成.
- 稳定性在较弱的有吸引力的蛋白质群体相互作用和较小的群体中更为明显.
- 由于排除体积效应,拥挤有利于形成球形和紧的二元体.
- 迪默的热力学稳定性高度依赖于群众的大小.
结论:
- 大分子拥挤增强了NmeCas9/AcrIIC3复合物的稳定性.
- 人群效应对人群大小和相互作用潜力敏感.
- 结果支持AcrIIC3.3.9对NmeCas9抑制的拟议机制.
相关概念视频
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