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APC/C的原子结构及其蛋白质无化机制
Leifu Chang1, Ziguo Zhang1, Jing Yang1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nature
|June 18, 2015
概括
酶促进复合体 (APC/C) 的结构研究揭示了Emi1如何抑制E2酶,并定义了Cdh1相互作用. 这为了解细胞分裂中的APC/C调控提供了一个框架.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 结构生物学 结构生物学
背景情况:
- 亚纳酶促进复合体 (APC/C) 是一个关键的E3泛基因酶,调节细胞周期过渡.
- APC/C活动受到协活性剂,酸化和检查点蛋白质的严格控制.
研究的目的:
- 为了确定APC/C-协同激活器复合物的原子结构.
- 阐明由Emi1抑制APC/C的机制以及由Cdh1调节的机制.
- 为了了解APC/C介导的无处不在反应.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得高分辨率的结构.
- 用Emi1和UbcH10-ubiquitin结合物的APC/C复合物的结构分析.
主要成果:
- 确定了APC/C-Emi1和APC/C-UbcH10-ubiquitin复合物的原子结构.
- 这些结构揭示了APC/C子单元和催化模块的架构.
- 定义了Emi1-介导的UbcH10和Ube2S抑制的机制.
- 阐明了Cdh1相互作用和Cdh1酸化的影响.
- 通过APC/C获得了关于APC/C启动无化过程的见解.
结论:
- 该研究提供了APC/C监管的详细结构理解.
- 这些发现为未来对APC/C功能的体内研究提供了定量框架.
- 这些结果进一步提高了我们对细胞周期控制和染色体分离的知识.
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