全球对N-终端氨酸依赖的降解机制的概况
Aizat Bekturova1, Yaara Makaros1, Shahar Ben-David1
1The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat Gan 5290002, Israel.
概括
在缺氧期间,Cys-Arg/N-degron通路调节蛋白质稳定性. 这种途径通过向像IP6K1这样的蛋白质来控制代谢适应和细胞存活,这对于在低氧条件下细胞能量生产至关重要.
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子生物学分子生物学
背景情况:
- 缺氧 (氧气不足) 给细胞带来压力,激活适应性生存机制.
- Cys-Arg/N-degron通路针对N端的囊蛋白进行降解,但其基质和在缺氧中的作用尚不清楚.
研究的目的:
- 为了确定Cys-Arg/N-degron通路的新基质.
- 为了阐明这一途径的基质特异性.
- 定义Cys-Arg/N-degron通路在细胞对低氧反应中的生物学作用.
主要方法:
- 使用N端子库对蛋白质稳定性的系统选.
- 突变性实验以确定途径的特异性.
- 在低氧条件下分析蛋白调节和细胞功能.
主要成果:
- 广泛的囊激活蛋白被确定为Cys-Arg/N-degron通路的基质.
- 该途径显示了对水和正电荷残留的特异性,其次是N端的氨酸.
- IP6K1被确定为低氧调节的基质;其损失损害了葡萄糖吸收,ATP生产和线粒体功能,破坏了代谢适应并减少了细胞存活率.
结论:
- 在低氧期间,Cys-Arg/N-degron通路在调节代谢反应方面发挥着重要作用.
- 这条通路对于细胞适应和在低氧压力下生存至关重要.
- 这种途径的失调可能会导致与缺氧相关的疾病.
相关概念视频
Regulated Protein Degradation
7.6K
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...
7.6K
The Proteasome
1.1K
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...
1.1K
Proteins: From Genes to Degradation
12.7K
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA...
Transcription is the synthesis of RNA...
12.7K
Covalently Linked Protein Regulators
7.2K
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....
7.2K
Export of Misfolded Proteins out of the ER
3.9K
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...
3.9K
Nuclear Export of mRNA
7.9K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.9K


