高速AFM成像显示了cohesin-NIPBL的DNA捕获和循环挤出动态
Parminder Kaur1, Xiaotong Lu2, Qi Xu3
1Physics Department, North Carolina State University, Raleigh, North Carolina, USA; Center for Human Health and the Environment, North Carolina State University, Raleigh, North Carolina, USA.
The Journal of biological chemistry
|September 29, 2023
概括
凝聚素-NIPBL复合体使用动态构造变化来捕获DNA,独立于ATP启动循环,并挤出DNA循环. 这揭示了一个新的多步骤DNA结合机制,这对于3D染色体组织至关重要.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物物理学的生物物理.
背景情况:
- 三维染色体组织对于基因调节和DNA过程至关重要.
- 凝聚蛋白复合体 (SMC1,SMC3,RAD21,SA1/SA2),与NIPBL一起,通过DNA循环挤出形成色素环.
- 凝聚素-NIPBL加载,循环启动和增长的机制仍然不清楚.
研究的目的:
- 阐明 DNA 结合和循环挤出过程中凝聚素-NIPBL 的动态构造变化.
- 为凝聚素-NIPBL DNA 结合机制提供直接实验证据.
主要方法:
- 高速原子力显微镜 (HS-AFM) 对凝聚素-NIPBL与DNA相互作用的成像.
- 对动态蛋白质构造变化和DNA结合事件的观察.
主要成果:
- 凝聚素-NIPBL通过手臂延伸和"脚" (突出) 捕获DNA,将其转移到其下部.
- DNA循环启动发生在二次DNA捕获时,独立于ATP水解.
- 显著的前向和反向DNA循环挤出步骤被可视化,由动态形状变化驱动.
结论:
- 为凝聚素-NIPBL建立了一个多步骤的DNA结合机制,涉及动态构造变化.
- 从SA1和NIPBL中确定"脚"对于DNA捕获和凝聚力加载至关重要.
- 进步对3D染色体组织和基因调节的分子基础的理解.
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