亚纳相促进复合物的分子结构和机制
Lei-Fu Chang1,2, Ziguo Zhang1,2, Jing Yang1,2
1Division of Structural Biology, Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK.
Nature
|July 22, 2014
概括
亚纳酶促进复合体/循环体 (APC/C) 通过无处化控制细胞分裂. 研究人员揭示了其完整的结构,揭示了联合激活剂如何调节其E3酶活性.
科学领域:
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
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,控制细胞循环的进展.
- 它的活动依赖于辅激剂子单元,但由于未知的子单元组织,其调节的结构基础仍然不明.
研究的目的:
- 确定人类APC/C-协活性剂-基质复合物的完整二级结构结构.
- 阐明了由协活性剂调节APC/C的分子机制.
主要方法:
- 在7.4 Å分辨率下,冷电子显微镜 (cryo-EM) 对人类APC/C-同活性剂-基质复合物的重建.
主要成果:
- 确定了完整的二级结构架构和1.2 MDa组件中所有20个APC/C子单元的最终位置.
- 确定了以前未被描述的子单元的蛋白质折叠.
- 在联合激活剂结合后观察到一个深刻的全转变,涉及催化子单元的位移和增加灵活性.
结论:
- 联合激活剂结合会诱导APC/C的显著构造变化,可能增强其E3酶活性.
- 这种结构洞察力为了解APC/C调节及其在细胞循环控制中的作用提供了分子基础.
更多相关视频
12:26Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
18.3K
08:33Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
Published on: December 5, 2017
13.7K
相关概念视频
Anaphase Promoting Complex
2.5K
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...
2.5K
Anaphase Promoting Complex
1.5K
1.5K
Separation of Sister Chromatids
3.6K
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...
3.6K
Anaphase A and B
4.3K
Microtubules form through the end-to-end polymerization of tubulin heterodimers. Kinetochore microtubules originate from the spindle poles, and their plus-ends connect with the kinetochores on sister-chromatids. Ndc80 protein complexes, present on the kinetochore, form low-affinity links with the plus end of these kinetochore microtubules.
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
Plus-end depolymerization releases tubulin heterodimers from the terminal region of the microtubule. As tubulin subunits are lost, the Ndc80 complexes detach...
4.3K
Anaphase A and B
4.7K
4.7K
The Spindle Assembly Checkpoint
2.9K
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...
2.9K
