相关实验视频
Updated: Jan 4, 2026

06:06
In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
5.9K
芬科尼贫血单联酶复合物的结构
Shabih Shakeel1, Eeson Rajendra1, Pablo Alcón1
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Nature
|November 1, 2019
概括
芬科尼贫血 (FA) 核心复合结构揭示了其在DNA修复中的作用. 对于基因组稳定性和癌症研究来说,了解这种E3泛素酶机制至关重要.
科学领域:
- 分子生物学
- 结构生物学
- 遗传学
背景情况:
- 芬科尼贫血 (FA) 途径对于修复DNA损伤,特别是交叉链接和响应复制压力至关重要.
- 在FA通路基因的突变导致发育问题,骨髓衰竭和癌症.
- FA核心复合物,一个E3泛酸酶,单聚化FANCD2-FANCI,是DNA修复的关键步骤.
研究的目的:
- 确定FA核心复合体的分子结构.
- 阐明FA核心复合体维持基因组稳定的机制.
主要方法:
- 一个活跃的,重组的FA核心复合物的复合.
- 用冷电子显微镜进行结构测定.
- 用于复杂分析的质谱学.
主要成果:
- FA核心复合体有一个扩展的,不对称的结构,中心是FANCB和FAAP100二极管,旁边是FANCL子单元.
- 尽管缺乏序列同样性,但FANCB和FAAP100具有相似的结构.
- FANCL的子单元呈现出不同的形状,表明不同的功能作用,并突出了该复合体的不对称性.
结论:
- 确定的结构为FA核心复合体在DNA跨链修复中的E3泛素连接酶活性提供了机制基础.
- 这些结构性见解解释了为什么FANCB,FANCL和FAAP100的突变是罕见的.
- 双面RING指域的不对称性可能是E3链酶的一般特征.
相关概念视频
Protein Complexes with Interchangeable Parts
2.8K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.8K
Protein Complexes with Interchangeable Parts
2.1K
2.1K
Electron Transport Chain: Complex I and II
18.3K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
18.3K
Anaphase Promoting Complex
3.3K
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...
3.3K
Protein Complex Assembly
16.5K
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
16.5K
Covalently Linked Protein Regulators
8.6K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
8.6K

