相关实验视频
Updated: Jul 16, 2025

06:06
In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
5.3K
通过全蛋白质组内部降解映射,阐明E3泛素酶特异性
Zhiqian Zhang1, Brandon Sie1, Aiquan Chang1
1Division of Genetics, Department of Medicine, Howard Hughes Medical Institute, Brigham and Women's Hospital, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Molecular cell
|September 22, 2023
概括
这项研究绘制了内部降解子的关键残留物,即E3结合酶识别的蛋白质降解信号,使用了一种全新型蛋白质组方法. 这些发现揭示了广泛的降解变异性,并为了解蛋白质调节提供了宝贵的资源.
科学领域:
- 分子生物学分子生物学
- 蛋白质组学是指蛋白质组学.
- 系统生物学 系统生物学
背景情况:
- 无素-蛋白酶体系统 (UPS) 对于细胞蛋白质平衡至关重要,通过E3无素连接酶调节蛋白质降解.
- 尽管E3结合酶数量很大 (约600个),但它们的基质识别特异性和它们识别的降解体尚不清楚.
- 识别和表征降解子对于理解UPS调节和开发有针对性的治疗方法至关重要.
研究的目的:
- 开发和应用一种蛋白质层级的策略,用于识别和绘制人体细胞中内部降解物质的关键残留物.
- 创建一个计算工具 (DegronID) 用于聚类和分析degron图案.
- 发现新的E3-degron相互作用并描述它们的结构决定因素.
主要方法:
- 全球蛋白质稳定性分析与机器学习相结合,可以预测含有降解子的.
- 扫描突变发生,以在预测的降解范围内识别关键残留物.
- 开发DegronID计算算法用于Degron动机集群.
- 基于CRISPR的查以识别E3降解体对.
主要成果:
- 确定了15,800种可能含有依赖序列的降解基的.
- 确定了超过5000个预测降解子的关键残留物,为219个Cullin-RING结合酶降解子产生突变指纹.
- 开发了DegronID,这是一个用于集群degron的计算工具.
- 发现了16种新的E3降解体对,揭示了显著的降解体变异性和结构特征.
结论:
- 这项研究提供了内部降解子及其关键残留物的全面蛋白质体规模地图.
- DegronID 促进了对降解基因和 E3 酶相互作用的分析和发现.
- 已识别的E3降解子对和相关数据为未来对蛋白质降解和调节的研究提供了宝贵的资源.
相关概念视频
Regulated Protein Degradation
7.4K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
7.4K
The Proteasome
873
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
873
Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K
Covalently Linked Protein Regulators
6.8K
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....
6.8K

