螺旋组装检查点的APC/C调节的分子基础
Claudio Alfieri1, Leifu Chang1, Ziguo Zhang1
1MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
Nature
|August 12, 2016
概括
螺旋组合检查点 (SAC) 防止细胞分裂的错误. 研究人员使用冷电子显微镜揭示了线粒检查点复合体 (MCC) 如何抑制亚相促进复合体 (APC/C),以确保精确的染色体分离.
科学领域:
- 细胞生物学
- 分子生物学
- 结构生物学
背景情况:
- 在细胞分裂过程中,螺旋组合检查点 (SAC) 对于精确的染色体分离至关重要.
- SAC通过抑制E3泛酶的泛酶促进复合体 (APC/C) 来预防过早的泛酶.
- 线性检查点综合体 (MCC) 是SAC的效应体,直接抑制APC/C活动.
研究的目的:
- 确定人类APC/CMCC复合物的近原子分辨率结构.
- 阐明MCC抑制APC/C活动的分子机制.
- 了解如何在SAC沉默时调节APC/C重新激活.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来获得APC/C(MCC) 复合物的高分辨率结构.
- 结构分析侧重于MCC子单元 (BubR1和Cdc20) 和APC/C组件之间的相互作用.
- 使用生物化学测定来研究该复合物的无处不在活性.
主要成果:
- 该结构揭示了MCC子单元BubR1如何阻断Cdc20上的关键位点,从而阻止APC/C基质的识别.
- 此外,BubR1还通过固体阻碍了E2酶UbcH10的结合,从而抑制了APC/ C的泛化.
- 规格的灵活性允许UbcH10结合,而Cdc20 (MCC) 的无处不在导致APC/C的重新激活.
结论:
- 该MCC使用双重机制来抑制APC/C:阻止Cdc20和阻止UbcH10的访问.
- 结构洞察力解释了MCC结合如何抑制APC/C活动以及如何缓解这种抑制.
- 了解这些机制为SAC功能和调节提供了分子基础.
更多相关视频
10:54Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
Published on: September 17, 2012
11.1K
13:59Studying Mitotic Checkpoint by Illustrating Dynamic Kinetochore Protein Behavior and Chromosome Motion in Living Drosophila Syncytial Embryos
Published on: June 14, 2012
11.9K
相关概念视频
02:19The Spindle Assembly Checkpoint
3.9K
The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
3.9K
02:19The Spindle Assembly Checkpoint
1.8K
1.8K
02:17Separation of Sister Chromatids
4.7K
At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
At the onset of anaphase, separase, a proteolytic enzyme, is...
4.7K
00:50Anaphase Promoting Complex
3.5K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
3.5K
00:50Anaphase Promoting Complex
1.8K
1.8K
02:36DNA Damage can Stall the Cell Cycle
10.3K
In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
10.3K