一个转录因子域蛋白质的非特异性与特定DNA结合的自由能量
Carmen Al Masri1, Biao Wan2, Jin Yu3
1Department of Physics and Astronomy, University of California, Irvine, California.
Biophysical journal
|October 28, 2023
概括
转录因子 (TFs) 结合DNA调节基因. 这项研究揭示了TF搜索和识别模式主要由蛋白质在DNA上的方向决定,这影响了基因调节的效率.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 计算生物学 计算生物学
背景情况:
- 转录因子 (TFs) 通过与特定的DNA位点结合来调节基因表达.
- 促进扩散模型描述了通过3D和1D扩散沿着DNA进行TF搜索.
- 在DNA结合过程中,TFs在搜索 (快速,非特定) 和识别 (稳定,特定) 模式之间切换.
研究的目的:
- 研究蛋白质定向在TF搜索和识别模式中的作用.
- 使用全原子分子动力学模拟来确定蛋白质-DNA结合的自由能量.
- 解释结合的自由能量和离散常数之间的差异.
主要方法:
- 全原子分子动力学模拟与转向力.
- 分析蛋白质-DNA结合的自由能量.
- 简化的球形蛋白-DNA模型与随机模拟和动力模型.
主要成果:
- 蛋白质在DNA上的定位区分了搜索和识别模式.
- 有约束力的自由能量差异显示出与解离常数测量的轻微偏差.
- 边缘DNA序列被确定为动力测量差异的潜在来源.
结论:
- 蛋白质定向是TF结合模式的关键决定因素.
- 结合动力学上的差异可能会受到侧面DNA序列的影响.
- 需要进一步的研究才能充分阐明TF-DNA相互作用的动态.
相关概念视频
Transcription Factors
76.0K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
76.0K
Cooperative Binding of Transcription Regulators
6.4K
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...
6.4K
Eukaryotic Transcription Activators
11.1K
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...
11.1K
General Transcription Factors
5.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
5.3K
RNA Polymerase II Accessory Proteins
9.2K
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
9.2K
Conserved Binding Sites
4.2K
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...
4.2K


