一项对Saccharomyces cerevisiae和人类酶促进复合体/环体 (APC/C) 的冷-EM结构的比较研究
Ester Vazquez-Fernandez1, Jing Yang1, Ziguo Zhang1
1MRC Laboratory of Molecular Biology, Cambridge, United Kingdom.
eLife
|October 14, 2024
概括
与人类的APC/C相比,酵母酶促进复合体/循环体 (APC/C) 的结构研究揭示了保存的架构,但与人类APC/C相比有不同的调节机制. 关键的区别涉及E2结合和辅激剂介导激活.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 细胞循环规则 细胞循环规则
背景情况:
- 亚纳酶促进复合体/循环体 (APC/C) 是一个关键的E3泛基因酶,调节细胞循环的进展.
- 虽然人类的APC/C结构得到了很好的研究,但酵母APC/C的研究仍然较少.
- 了解跨物种的APC/C变异,可以了解保护和分歧的监管策略.
研究的目的:
- 为了确定关键的*Saccharomyces cerevisiae*APC/C复合物的中等分辨率结构.
- 为了比较酵母APC/C的结构和调节机制与其人类对应物.
- 阐明联合激活剂结合和酸化依赖调节的差异.
主要方法:
- 三种*S. cerevisiae*APC/C复合物的中等分辨率结构确定:非酸化的apo-APC/C,酸化的apo-APC/C,以及APC/CCDH1-基质复合物.
- 酵母和人类APC/C复合体之间的比较结构分析.
- 对酸化依赖性调节和辅激剂介导的E2结合的研究.
主要成果:
- 人类和酵母APC/C的整体结构被保留,包括通过CDK酸化抑制CDH1.
- 通过酸化观察到协活性剂刺激的E2结合和APC/CCDC20激活的显著差异.
- 酵母Apo-APC/C的催化模块预先定位为E2结合,与人类APC/C不同.
- 在酵母APC1中缺少可调节的自身抑制细分,与人类APC/C.形成鲜明对比.
结论:
- 虽然APC/C功能在酵母和人类中保持不变,但特定的调节分子机制有所不同.
- 结构变化突出了控制E2结合和协同激活器参与的不同策略.
- 这些发现加深了我们对细胞周期控制多样化在真核细胞的理解.
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