卷-卷-域介导的TRIM E3蛋白质凝结调节酶活性和功能特异性
1College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang, China; School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
Cell reports
|June 1, 2025
概括
大多数三方基因 (TRIM) 蛋白质形成生物分子凝聚物,影响E3结合酶活性和细胞功能. 卷轴-卷轴域对于这种凝结至关重要,与疾病相关的变异会损害该过程.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 三方基因 (TRIM) 蛋白质是具有模块化结构的E3无素连接酶.
- TRIM蛋白涉及到各种细胞过程.
- 生物分子凝聚在调节TRIM蛋白功能的作用在很大程度上是未知的.
研究的目的:
- 系统地研究TRIM蛋白质形成生物分子凝聚物的能力.
- 为了确定TRIM冷凝的结构元素和功能后果.
- 探索TRIM凝结物的细胞作用和疾病相关性.
主要方法:
- 在哺乳动物细胞中对75种TRIM蛋白进行系统检查.
- 分析了线圈-线圈 (CC) 域在凝结中的作用.
- 在体外和细胞测试以评估E3结合酶活性调节.
- 对TRIM凝结物的蛋白质组分析.
- 在细胞组织中TRIM凝聚剂作用的功能选.
主要成果:
- 大多数TRIM蛋白可以单独形成或共同凝结.
- CC域对于TRIM凝聚是必不可少的;与疾病相关的SNP破坏了这一点.
- 凝结以取决于环境的方式调节TRIM E3结合酶活性.
- 在21个TRIM凝聚物中的蛋白质与关键的细胞通路和疾病有关.
- 特定的TRIM凝聚物调节心状卫星组织,乳毛组合和微管稳定.
结论:
- 生物分子凝结是TRIM蛋白的广泛调节机制.
- 特别是通过CC域的TRIM凝结对于细胞功能和疾病至关重要.
- 这项研究为了解TRIM蛋白质凝聚和共凝聚特异性建立了框架.
相关概念视频
Covalently Linked Protein Regulators
7.5K
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....
7.5K
Conservation of Protein Domains Over Different Proteins
11.5K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
11.5K
Conserved Binding Sites
4.4K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.4K
Protein Folding
121.9K
Overview
121.9K
Condensins
3.7K
Condensins are large protein complexes that use ATP to fuel the assembly of chromosomes during mitosis. They transform the tangled, shapeless mass of post-interphase DNA into individualized chromosomes by compacting, organizing, and segregating chromosomal DNA.
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
The plant and animal cells contain two types of condensin complexes—condensin I and condensin II. Both complexes have five subunits: two SMC (Structural Maintenance of Chromosomes) subunits, a kleisin subunit, and two HEAT-repeat...
3.7K
Cooperative Binding of Transcription Regulators
6.6K
Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome. Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
6.6K


