细胞外蛋白质稳定在致病性攻击期间防止聚合
Ivan Gallotta1, Aneet Sandhu1,2, Maximilian Peters3
1German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Nature
|July 10, 2020
概括
科学家发现了C. elegans中调节细胞外蛋白聚合的网络. 这种细胞外蛋白质稳定网络在增强时会增强宿主的防御能力,延缓衰老,增加对毒素的抵抗力.
科学领域:
- 分子生物学
- 细胞生物学
- 免疫学
背景情况:
- 这种分泌的蛋白质对细胞间的交流,天生的免疫力和细胞外矩阵的形成至关重要.
- 与细胞内空间相比,细胞外环境对蛋白质构成更严峻的条件,有限的ATP可用性阻碍了蛋白质质量控制.
- 已知防止蛋白质聚合的细胞外伴侣和蛋白质酶是有限的.
研究的目的:
- 系统地分析Caenorhabditis elegans中的细胞外蛋白质稳定网络.
- 确定细胞外蛋白聚合的调节剂.
- 研究细胞外蛋白质稳定对病原体的反应及其对宿主防御和衰老的影响.
主要方法:
- 一个大规模的RNA干扰屏幕,针对C. elegans中分泌的蛋白质编码基因.
- 使用形成毛孔的毒素模仿病原性攻击,以评估细胞外蛋白质稳定反应.
- 研究所涉及的信号通路,特别是压力激活的MAP激酶信号.
主要成果:
- 发现了57种细胞外蛋白聚合的调节剂,其中一些与先天免疫有关.
- 在受孔形成毒素的作用下,C. elegans提高了细胞外蛋白质稳定成分的调节,并降低了蛋白质聚合.
- 细胞外蛋白质稳定的激活取决于压力激活的MAP激酶信号.
- 细胞外蛋白质稳定成分的过度表达会延缓衰老,并赋予抗毒性.
结论:
- 细胞外蛋白质稳定是一种对病原性刺激作出反应的活跃网络.
- 通过保持分泌的蛋白质组完整性和预防蛋白质毒性,增强的细胞外蛋白质稳定有助于系统性宿主防御.
- 这种网络在宿主防御,衰老和对毒素的抵抗中起作用.
相关概念视频
The Proteasome
1.4K
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...
1.4K
The Proteasome
9.9K
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...
9.9K
Amyloid Fibrils
11.4K
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining,...
11.4K
Molecular Chaperones and Protein Folding
19.3K
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
19.3K
Regulated Protein Degradation
8.5K
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...
8.5K
Regulated Protein Degradation
2.9K
2.9K


