在一个非结构化的区域中,通过多个酸盐对Ets-1DNA结合的可变控制
Miles A Pufall1, Gregory M Lee, Mary L Nelson
1Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City, UT 84112-5550, USA.
Science (New York, N.Y.)
|July 5, 2005
概括
在Ets-1转录激活器上,多个酸化点就像一个静体,通过分级细胞信号来微调DNA结合亲和力. 这种翻译后修改改变了蛋白质构造,影响了基因转录.
科学领域:
- 分子生物学分子生物学
- 生物化学 生物化学
- 细胞信号传递 细胞信号传递
背景情况:
- 翻译后的修改,如酸化,对于调节蛋白质活性至关重要.
- 像Ets-1这样的转录因子在基因表达中起着关键作用,但它们的调节是复杂的.
研究的目的:
- 研究Ets-1蛋白质上的依赖的酸化位如何影响其DNA结合亲和力.
- 阐明Ets-1酸化在细胞信号传递中的结构和功能后果.
主要方法:
- 核磁共振 (NMR) 光谱法被用来分析在酸化后Ets-1中的结构变化.
- 该研究的重点是Ets-1蛋白内的Ca2+依赖酸化位.
主要成果:
- 发现,Ets-1上的多个酸化点具有附加作用,导致DNA结合亲和力的分级变化.
- 核磁共振分析显示,酸化诱导了从动态的转变,DNA结合-ready conformation到一个很好的折叠,抑制状态.
- 化部位位于一个灵活的区域,作为一个全效应器,调解自身抑制.
结论:
- 变量化Ets-1的功能作为一个分子静电,提供一个微调转录的机制.
- 这项研究揭示了一种新的转录因子在DNA结合水平的调节机制,通过酸化控制全菌.
相关概念视频
00:58DNA Packaging
Overview
01:46Epigenetic Regulation
Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
02:04Covalently Linked Protein Regulators
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein.
These groups modify specific amino acids in a protein.
02:32Histone Modification
The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
Acetylation
The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone deacetylase,...
02:13Cooperative Binding of Transcription Regulators
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 dimers that...
01:37Epigenetic Regulation
Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
X-chromosome...