溶液核磁共振结构和基于核磁共振的UbKEKS的分子骨干动力学:一种在UBB4假基因中编码的泛素变体,具有新兴的特定和新功能
Patrick Delattre1,2,3, Danny Létourneau2,4, Anna Meller5,6
1Faculté de médecine et des sciences de la santé, Département de Biochimie et de Génomique Fonctionnelle, Université de Sherbrooke, 3001 12e Avenue Nord, Sherbrooke, QC J1H 5N4, Canada.
Biochemistry and cell biology = Biochimie et biologie cellulaire
|October 2, 2025
概括
一种新型的ubiquitin (Ub) 变体,UbKEKS,从伪基因表达出来,不会触发蛋白质降解. 结构和动态分析揭示了其独特特征如何改变基质相互作用和功能.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 蛋白质组学是指蛋白质组学.
背景情况:
- 乌比基因 (Ub) 变体可以从伪基因表达出来,从而产生新的功能.
- 伪基衍生的Ub变体UbKEKS与正规的Ub不同,并不会通过K48链接促进蛋白质体降解.
研究的目的:
- 与正规的Ub.相比,阐明UbKEKS独特的功能性质的结构和动态基础.
主要方法:
- 对 UbKEKS的NMR溶液结构的确定.
- 使用15N-放松的UbKEKS骨干动态的表征.
- 对残留物特定的形状变化和运动的分析.
主要成果:
- UbKEKS 保持了规范的螺旋抓折叠,但在子模式调节残留物中表现出显著的重新排列和放大运动.
- 突变Q2K和K33E增强了关键调节区域的ps-n和μs-ms时间表运动.
- 突变Q49K影响UIM识别,可能会损害K48链形成和蛋白质酶体结合.
结论:
- 在 UbKEKS 的结构和动态差异解释了其改变的基质形状.
- 鉴定到的决定因素解释了UbKEKS无法针对蛋白质进行蛋白质体降解的原因.
相关概念视频
Covalently Linked Protein Regulators
8.7K
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....
8.7K
Protein Complexes with Interchangeable Parts
2.9K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
2.9K
The 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
The Proteasome
10.1K
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...
10.1K
The 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
Regulated Protein Degradation
8.7K
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...
8.7K


