亚相促进复合物的子单元组件的结构基础
Anne Schreiber1, Florian Stengel, Ziguo Zhang
1Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK.
Nature
|February 11, 2011
概括
亚纳酶促进复合体 (APC/C),一个大型的E3泛基因酶,其结构已经揭示出来. 这项研究定义了其子单元的组织和相互作用,为70%的复合体提供了伪原子模型.
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:
- 亚纳酶促进复合体或循环体 (APC/C) 是一个关键的E3泛基因酶,调节细胞周期过渡.
- 对APC/C组件和子单元相互作用的详细理解仍然有限.
研究的目的:
- 使用重组表达系统重组Holo APC/C及其子复合体.
- 确定APC/C子单位的精确组织和结构及其相互作用.
主要方法:
- 重组表达和复合APC/C和子复合物的复合.
- 低温电子显微镜和质谱学.
- 结晶学和同质学衍生的坐标的对接.
主要成果:
- 对70%的APC/C产生了一个伪原子模型,揭示了它的格子状结构.
- 三个保存的四基重复 (TPR) 子单元 (Cdc16,Cdc23,Cdc27) 形成了一个准对称的结构.
- 脚手架子单位协调催化模块,基板识别模块和监管站点.
结论:
- 这项研究为APC/C复合体提供了前所未有的结构洞察力.
- 定义的结构阐明了APC/C子单元如何组装和与监管因素相互作用.
- 这项工作为了解细胞循环调节中的APC/C功能奠定了基础.
相关概念视频
Anaphase Promoting Complex
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...
Anaphase Promoting Complex
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...
Separation of Sister Chromatids
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...
Spindle Assembly
Spindle assembly occurs through three, often coexisting, pathways – the centrosome-mediated pathway, the chromatin-mediated pathway, and the microtubule-mediated pathway – collectively contributing to form a robust spindle apparatus.
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a microtubule array...
In most cells, centrosomes are the primary microtubule nucleation centers. In the centrosome-mediated pathway, the G2-prophase transition triggers centrosome maturation and increased microtubule nucleation. Progressive nucleation results in a microtubule array...
Anaphase A and B
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...
Anaphase A and B
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...


