系统的DNA窃取揭示了蛋白质识别的结构逻辑
Yumi Minyi Yao1, Michael P O'Hagan1, Karn Onoon2
1Department of Chemical and Structural Biology, Weizmann Institute of Science, Rehovot 7610001, Israel.
bioRxiv : the preprint server for biology
|July 9, 2025
概括
DNA的骨干结构,而不仅仅是序列,决定了转录因子的结合. 新的方法揭示了DNA机制是基因调节的关键,将重点从基因身份转移到物理架构.
科学领域:
- 分子生物学分子生物学
- 生物物理学的生物物理.
- 基因组学就是基因组学.
背景情况:
- 转录因子 (TFs) 通过结合特定的DNA位点来调节基因表达.
- TF-DNA的识别取决于基序和DNA的结构性质,如变形和拉伸.
- 由于以序列为中心的方法,当前的研究往往忽略了DNA结构决定因素.
研究的目的:
- 开发一种方法来研究TF结合的DNA结构决定因素,独立于基序.
- 系统地探测DNA机制如何影响TF-DNA识别.
主要方法:
- 引入了PIC-NIC,这是一种高通量策略,可以在TF绑定站点中创建单链断裂 (SSB),而不会改变基序.
- 在引入nicks后,量化测量TF结合亲和力和特异性变化.
- 集成的实验数据与高分辨率的晶体结构和分子动力学模拟.
主要成果:
- 确定了TF结合关键的特定骨干位置,其中nick可以取消,改变或增强结合.
- 证明了DNA机制,包括骨干几何和连续性,独立地塑造结合特异性.
- 展示了TF-DNA识别受到不仅仅是线性基序的影响.
结论:
- DNA骨干结构是TF-DNA识别的关键功能决定因素,而不仅仅是一个被动的支架.
- 这些发现挑战了以序列为中心的范式,突出了DNA机制在基因调节中的作用.
- 这项工作为管理TF-DNA相互作用和基因调节的原则提供了新的见解.
相关概念视频
01:03Single-Strand DNA Binding Proteins
15.0K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
15.0K
01:16The DNA Helix
143.7K
Overview
143.7K
01:11Restriction Enzymes
31.4K
Restriction enzymes are bacterial enzymes used to cut DNA in a sequence-specific manner. To cleave DNA, they bind to specific palindromic sequences called restriction sites. Such palindromic DNA sequences or inverted repeats are commonly found in regions of functional significance, such as the origin of replication, gene operator sites, and regions containing transcription termination signals.
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
The host bacteria protect their own genomic DNA from these enzymes by methylating these sites. Some...
31.4K
02:31Homologous Recombination
52.4K
The basic reaction of homologous recombination (HR) involves two chromatids that contain DNA sequences sharing a significant stretch of identity. One of these sequences uses a strand from another as a template to synthesize DNA in an enzyme-catalyzed reaction. The final product is a novel amalgamation of the two substrates. To ensure an accurate recombination of sequences, HR is restricted to the S and G2 phases of the cell cycle. At these stages, the DNA has been replicated already and the...
52.4K
02:05DNA as a Genetic Template
22.9K
Two structural features of the DNA molecule provide a basis for the mechanisms of heredity: the four nucleotide bases and its double-stranded nature. The Watson-Crick model of double-helical DNA structure, proposed in 1952, drew heavily upon the X-ray crystallography work of researchers Rosalind Franklin and Maurice Wilkins. Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their work in 1962. Franklin was, controversially, excluded from the prize for...
22.9K
03:06From DNA to Protein
19.2K
The flow of genetic information in cells from DNA to mRNA to protein is described by the central dogma, which states that genes specify the sequence of mRNAs, which in turn specify the sequence of amino acids making up all proteins. The decoding of one molecule to another is performed by specific proteins and RNAs. Because the information stored in DNA is so central to cellular function, it makes intuitive sense that the cell would make mRNA copies of this information for protein synthesis...
19.2K