在CITED转录激活域的构造组合中的序列编码差异会影响联合激活剂结合
bioRxiv : the preprint server for biology
|February 6, 2026
概括
像CITED蛋白一样,内在无序的蛋白质 (IDP) 调节转录. 细微的序列变化显著改变了它们的结构和动态,影响了与其他蛋白质的关键相互作用.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子生物学分子生物学
背景情况:
- 内在无序的蛋白质 (IDP) 缺乏稳定的3D结构,这对理解序列功能关系构成挑战.
- CITED 蛋白质是有保留 C 终端交换激活域 (CTAD) 的无序转录调节器,它们与 CBP/p300 TAZ1 域结合.
- 已知CITEDCTAD中的氨基酸替代物会影响TAZ1结合,但它们对不同CITED家族成员的影响尚不清楚.
研究的目的:
- 调查CITED CTADs中的序列变化如何影响它们的构造组合,动态和与TAZ1域的相互作用.
- 通过实验来描述CITED1,CITED2和CITED4CTAD的结构和动态特性.
主要方法:
- 溶液核磁共振 (NMR) 谱学用于研究构造组合和动态.
- 循环二元化 (CD) 光谱法用于评估蛋白质结构.
- 表面等离子共振 (SPR) 用于量化结合热力学和动力学.
主要成果:
- 单独地,CITED CTADs是失序的,CITED2 CTAD独特地显示了对离子强度和度敏感的残余螺旋结构.
- 在CITED1和CITED4中,CTAD表现出更加统一的动态,并且在很大程度上保持无序.
- 对TAZ1的结合亲缘关系有很大的不同,CITED2显示最强的相互作用,CITED4显示最弱的相互作用.
结论:
- IDP 形状合集对微妙的序列改变非常敏感.
- IDP结构和动态的变化直接影响它们的生物功能,特别是蛋白质-蛋白质相互作用.
- 这项研究提供了关于IDP中的序列结构功能关系的关键实验数据.
更多相关视频
相关概念视频
Eukaryotic Transcription Activators
12.8K
Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These...
12.8K
Cooperative Binding of Transcription Regulators
7.4K
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...
7.4K
Cooperative Binding of Transcription Regulators
2.6K
2.6K
Prokaryotic Transcriptional Activators and Repressors
25.5K
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
25.5K
Eukaryotic Transcription Inhibitors
11.0K
Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
11.0K
Conserved Binding Sites
5.2K
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...
5.2K


