在B-raf基因中的促进子序列的晶体结构揭示了交织在一起的二元四重复
Dengguo Wei1, Alan K Todd, Mire Zloh
1UCL School of Pharmacy, University College London , London WC1N 1AX, United Kingdom.
Journal of the American Chemical Society
|December 4, 2013
概括
研究人员在B-raf基因促进器中发现了一种不寻常的二维四重复结构. 这种由离子稳定的DNA结构对理解基因调节和潜在的治疗点有影响.
科学领域:
- 结构生物学 结构生物学
- 基因组学就是基因组学.
- 生物化学 生物化学
背景情况:
- 该B-raf基因促进体包含一个特定的DNA序列 (d(GGGCGGGGGGGGGGGGAAGGGA)).
- 促进器区域对于基因调节至关重要.
- 基因四重组是非规范性结构,在细胞过程中具有潜在的作用.
研究的目的:
- 为了确定B-raf基因促进体中发现的DNA序列的三维结构.
- 为了研究这种DNA结构在离子存在时的形成和稳定性.
- 探索人类基因组中类似结构的潜力.
主要方法:
- 进行X射线晶体学以阐明高分辨率结构.
- 溶液紫外线和循环二极化谱法,以评估结构稳定性.
- 1D核磁共振 (NMR) 和凝电泳以研究溶液中的物种.
- 分子建模以构建单链分子内四重复.
- 人类基因组数据库搜索以确定类似的序列.
主要成果:
- B-raf促进子序列形成了一个前所未有的二维四重复结构.
- 该结构具有七个G四重奏的核心和六个离子的不间断运行.
- 它表现出一个扭曲的G·C·G·C基四重奏和四个翻转的腺核化物.
- 溶液研究证实了稳定的四重排列,并指出二聚物是溶液中占主导地位的物种.
- 分子建模成功地从二元结构中创建了一个单链分子内四重复.
- 基因组分析揭示了许多人类序列,这些序列有可能形成类似的分子内四重复.
结论:
- B-raf 基因促进序列采用了独特的二维四重复形状.
- 这种结构由离子稳定,并表现出不寻常的特征.
- 这些发现表明,分子内四重复可能在人类基因组中普遍存在.
- 这种结构可以在基因调节和疾病中发挥重要作用.
- 这项研究为了解基因促进体中的四重复形成提供了结构基础.
相关概念视频
02:13Cooperative Binding of Transcription Regulators
6.0K
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...
6.0K
02:40The Eukaryotic Promoter Region
16.2K
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...
16.2K
02:40The Eukaryotic Promoter Region
3.4K
3.4K
01:53Bacterial Transcription
25.6K
RNA polymerase (RNAP) carries out DNA-dependent RNA synthesis in both bacteria and eukaryotes. Bacteria do not have a membrane-bound nucleus. So, transcription and translation occur simultaneously, on the same DNA template.
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
Transcription can be divided into three main stages, each involving distinct DNA sequences to guide the polymerase. These are:
25.6K
01:47Transcription Initiation
17.0K
Initiation is the first step of transcription in eukaryotes. Prokaryotic RNA Polymerase (RNAP) can bind to the template DNA and start transcribing. On the other hand, transcription in eukaryotes requires additional proteins, called transcription factors, to first bind to the promoter region in the DNA template. This binding helps recruit the specific RNAP that can assemble on the DNA and start transcription.
The promoters and enhancers and their accessory proteins allow tight regulation of...
The promoters and enhancers and their accessory proteins allow tight regulation of...
17.0K
01:07MAPK Signaling Cascades
7.3K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
7.3K