由26S蛋白酶体降解基质的机制和调节
Connor Arkinson1,2,3, Ken C Dong3, Christine L Gee1,2,3
1California Institute for Quantitative Biosciences, University of California at Berkeley, Berkeley, CA, USA.
Nature reviews. Molecular cell biology
|October 3, 2024
概括
26S蛋白酶体通过特定和乱交的机制调节蛋白质降解. 本综述探讨了基质识别,ATP依赖性降解和调节剂,为疾病治疗策略提供了信息.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 26S蛋白酶对真核细胞中的蛋白质稳态至关重要.
- 蛋白质降解需要在特异性和杂乱性之间保持平衡.
研究的目的:
- 审查基质识别和由蛋白质酶体依赖ATP降解的原理.
- 讨论最近关于无素依赖和无素独立蛋白质循环的见解.
- 探索蛋白质酶调节器和通过p97开发的上游处理.
主要方法:
- 关于蛋白酶体研究近期进展的文献综述.
- 对基质识别和降解机制的分析.
- 综合有关蛋白质酶体功能和调节的信息.
主要成果:
- 详细讨论无素依赖和无素独立的蛋白质循环.
- 识别影响蛋白质酶功能的各种调节剂 (辅因子,酶,二维基酶).
- 概述p97在基质加工中发挥的作用.
结论:
- 了解蛋白酶体结构和功能方面的进步为新的治疗策略提供了机会.
- 有针对性的抑制或利用蛋白酶体活性可以治疗人类疾病.
- 蛋白质溶解的目标是嵌合体和分子是有前途的治疗方法.
相关概念视频
Regulated Protein Degradation
7.2K
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...
7.2K
The Proteasome
8.5K
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...
8.5K
The Proteasome Structure
716
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...
716
Regulation of Expression at Multiple Steps
875
The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
875
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
Proteins: From Genes to Degradation
12.1K
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...
12.1K


