相关实验视频
Updated: Jul 15, 2025

06:06
In Vitro Analysis of E3 Ubiquitin Ligase Function
Published on: May 14, 2021
5.3K
在膜上RING E3泛基因酶TRIM72的结构和激活
Si Hoon Park1,2, Juhyun Han1, Byung-Cheon Jeong1,3
1Department of Life Sciences, Korea University, Seoul, South Korea.
Nature structural & molecular biology
|September 28, 2023
概括
血维修缺陷与肌肉和心脏疾病有关. 这项研究揭示了三方基因含有蛋白72 (TRIM72) 在受损膜上如何组合,为E3结合酶调节和潜在的治疗策略提供了洞察力.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 细胞生物学 细胞生物学
背景情况:
- 血维修缺陷与人类肌肉和心脏疾病有关.
- 三方基因含蛋白72 (TRIM72),也称为mitsugumin 53 (MG53),对于膜损伤部位的快速囊泡核形成至关重要.
- 控制TRIM72在膜修复中的功能的精确分子机制尚未完全理解.
研究的目的:
- 为了阐明TRIM72在血修复中的分子机制.
- 为了呈现Mus musculus TRIM72的结构模型,一个完整的TRIM E3无酸酶.
- 研究膜相互作用在TRIM72的组装和活动中的作用.
主要方法:
- 进行X射线晶体学以确定TRIM72.2.的结构.
- 低温电子断层扫描和亚断层扫描的平均值可用于可视化脂双层上高阶TRIM72组件.
- 生物化学测试以评估TRIM72-膜相互作用和无处不在活性.
主要成果:
- 在TRIM72和富含脂胺的膜之间的相互作用对于其寡合组合和E3无素酶活性至关重要.
- 使用冷电子断层扫描阐明了脂双层上的TRIM72组件的更高阶模型.
- 开发了TRIM72的综合分子模型,突出了对RING型E3酶调节的更高阶组合中的域合作.
结论:
- 这项研究为理解TRIM E3结合酶提供了基本的结构和机制基础.
- 这些发现提供了关于TRIM72如何通过对受损膜的寡合组合来调节E3酶活性的见解.
- 这项研究对与血膜修复受损相关的疾病具有显著的治疗意义.
相关概念视频
The Unfolded Protein Response
4.7K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.7K
Protein Translocation Machinery on the ER Membrane
4.7K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
4.7K
Export of Misfolded Proteins out of the ER
3.6K
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...
3.6K
Rab Proteins
4.0K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.0K
Regulated Protein Degradation
7.4K
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...
7.4K
The Proteasome Structure
788
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...
788

