蛋白质无处不在化所需的长时间SPOP结合降解子的序列规则
Linda Makhlouf1, Mukul Mishra2, Hannah Makhlouf1
1Astbury Centre for Structural Molecular Biology, School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
The Biochemical journal
|April 3, 2025
概括
斑点型BTB/POZ蛋白 (SPOP) 针对蛋白质进行降解. 研究人员发现了一种新的Q动机,它与已知的共识一起,控制了SPOP如何结合和无处不在的基质,如MyD88.8.
科学领域:
- 分子生物学分子生物学
- 蛋白质降解 蛋白质降解
- 在Ubiquitination中使用.
背景情况:
- 斑点型BTB/POZ蛋白 (SPOP) 是一种适应蛋白,对基于库林-3的E3酶的选择性蛋白质无处不在至关重要.
- 骨髓分化主响应88 (MyD88) 是由基于SPOP的E3链酶无处不在,负面调节免疫信号,但精确的结合规则尚不清楚.
研究的目的:
- 阐明控制SPOP介导基质识别和降解的序列规则.
- 确定SPOP-基底相互作用的新型结合动机和结构决定因素.
主要方法:
- 生物化学试验用于研究蛋白质与蛋白质相互作用.
- 基于哺乳动物细胞的实验,以评估已识别的图案的作用.
- 进行X射线晶体学以确定SPOP-基质结合的结构基础.
主要成果:
- MyD88通过含有已知的共识和新发现的N终端Q动机的长降解与SPOP相互作用.
- 其他基板,包括SRC-3,SETD2和Caprin1,也通过这种机制参与SPOP.
- Q-motif对于哺乳动物细胞中的SPOP相互作用至关重要,其结构基础通过X射线结晶学确定.
结论:
- 一个新的共识序列,Q-motif,扩展了SPOP基质结合的已知规则.
- 这一发现对于理解SPOP介导的E3酶基质识别和随后的无处不在和降解至关重要.
相关概念视频
Regulated Protein Degradation
7.1K
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...
7.1K
Covalently Linked Protein Regulators
6.7K
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....
6.7K
The Proteasome
8.4K
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...
8.4K
Directing Proteins to the Rough Endoplasmic Reticulum
6.9K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
6.9K
Regulation of Nuclear Protein Sorting
2.3K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.3K
Regulation of Expression at Multiple Steps
850
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...
850


