从罕见但在进化上保存的域组合中识别膜结合的转录调节蛋白
Muyoung Lee1, Yeejin Jang1, Qingqing Guo1
1Department of Molecular Bioscience, The University of Texas at Austin Austin, TX 78712, United States.
bioRxiv : the preprint server for biology
|December 25, 2025
概括
研究人员使用生物信息学屏幕发现了新的膜结合转录调节器 (MBTRs). 这种方法识别了将外部信号与核反应集成的蛋白质,扩大了我们对基因调节的理解.
科学领域:
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
- 细胞生物学 细胞生物学
背景情况:
- 转录因子 (TFs) 调节核内的基因表达.
- 一些TFs,称为膜结合转录因子 (MBTFs),在核转位之前被固定在细胞膜中.
- 已知的MBTF如MYRF和SREBP对于重要细胞过程至关重要,但它们的全部多样性尚不清楚.
研究的目的:
- 开发一个生物信息学屏幕来识别新的膜结合转录调节器 (MBTRs).
- 调查MBTR的多样性和功能,超出已知的例子.
- 探索膜蛋白如何将细胞外信号与核转录反应集成.
主要方法:
- 开发了一种生物信息学方法,用于选潜在的转录调节功能的膜蛋白.
- 杆域组合分析,寻找跨膜域与转录调节域的保守配对.
- 利用与重组蛋白质的测试来验证预测的MBTR并确定跨膜域在亚细胞局部化中的作用.
主要成果:
- 选方法成功识别了已知的MBTF和膜结合的基因素激酶.
- 发现了新的MBTR候选物质,包括跨膜基因素N-乙转移酶和益生素调节元素结合蛋白 (PREB).
- 证明PREB的跨膜域决定了它在小鼠胚胎干细胞中的细胞膜和细胞核之间的定位.
结论:
- 生物信息学屏幕对于识别新型MBTRs是有效的.
- 确定了MBTF和PREB等新型调节蛋白的潜在新子类.
- 为未来研究参与信号集成和转录调节的MBTR提供了一个框架.
相关概念视频
01:49Conserved Binding Sites
5.0K
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...
5.0K
02:13Cooperative Binding of Transcription Regulators
7.1K
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...
7.1K
02:13Cooperative Binding of Transcription Regulators
2.4K
2.4K
02:02Cis-regulatory Sequences
11.5K
Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
11.5K
02:02Cis-regulatory Sequences
3.9K
3.9K
02:23Master Transcription Regulators
7.6K
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
7.6K