模拟液-液相分离及其对蛋白质体基质降解降解的影响
Di Wu1, Qi Ouyang2, Hongli Wang1,3
1The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing, China.
Computational and structural biotechnology journal
|December 4, 2025
概括
由RAD23B调节的蛋白质体液液相分离 (LLPS) 影响蛋白质降解. 这项研究模拟了LLPS动态及其对蛋白质体降解效率的上下文影响.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- 蛋白质酶体对于通过ubiquitin-proteasome系统降解蛋白质至关重要.
- 蛋白质酶相关的液态液态相分离 (LLPS) 在基质加工过程中发生,但其机制和功能作用尚不清楚.
- 敏感于辐射的23同源B (RAD23B) 是一个基质穿因子,参与蛋白质体降解.
研究的目的:
- 量化描述由RAD23B介导的蛋白酶相关的LLPS.
- 阐明LLPS在蛋白质酶介导降解中的调节机制和功能作用.
- 开发一个对蛋白质体LLPS动态的预测模型.
主要方法:
- 使用热力学约束的反应-扩散模型的开发.
- 蛋白酶相关的LLPS动态的定量表征.
- 分析LLPS对蛋白质酶介导降解效率的影响.
主要成果:
- 该模型成功地捕获了实验LLPS动态.
- 确定了一种度依赖的相位过渡边界,受蛋白酶体活性和分子相互作用的影响.
- 现实中,LLPS在降解效率上表现出双向的,取决于环境的影响,增强或抑制降解效率.
结论:
- 在蛋白质酶介导的蛋白质降解中,LLPS是关键的调节机制.
- 该研究提供了蛋白质体LLPS的定量模型,提供了可测试的假设.
- 了解LLPS在蛋白质体功能中的理解对于阐明细胞蛋白质平衡至关重要.
相关概念视频
01:13The Proteasome
1.6K
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...
1.6K
02:18The Proteasome
10.0K
Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst 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. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
10.0K
01:17The Proteasome Structure
1.6K
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
The proteasome is an...
1.6K