在DNA上配对 (Pax) 类合作性宿主体二次体的高分辨率晶体结构
D S Wilson1, B Guenther, C Desplan
1Laboratories of Molecular Biophysics, Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021, USA.
Cell
|September 8, 1995
概括
配对的家庭主体 (Pax) 蛋白质以二分体的形式合作地结合DNA. 水分子和DNA扭曲促进了这种相互作用,使特定的目标序列识别成为可能.
科学领域:
- 结构生物学 结构生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 家庭主体是调节基因表达的关键转录因子.
- 配对 (Pax) 类家庭主域与DNA结合,控制发育过程.
- 了解合作性DNA结合是解读基因调节特异性的关键.
研究的目的:
- 为了确定与DNA结合为合作二次体的配对家庭主域的晶体结构.
- 阐明Pax家庭主体中合作性DNA结合背后的分子机制.
- 研究水分子和DNA变形在这种相互作用中的作用.
主要方法:
- 在2.0A分辨率的X射线晶体学.
- 蛋白质-DNA相互作用的结构分析.
- 用单体家庭主体-DNA复合体进行比较结构分析.
主要成果:
- 晶体结构揭示了直接的家庭主体-DNA接触和广泛的水介导接口.
- 同源域和必要的DNA变形之间的对称接触促进了合作结合.
- 一个单一的家庭主体结合可以预先扭曲DNA,为第二个家庭主体的合作相互作用做好准备.
结论:
- 帕克斯家庭域在没有辅助域的情况下,本质上实现了DNA结合合作.
- 这种机制允许识别较长的DNA序列,确保高目标特异性.
- 这些发现提供了对转录因子结合的演变和功能的见解.
相关概念视频
The DNA Helix
Overview
Gene Families
Gene families consist of groups of genes proposed to have originated from a common ancestor. Typically these arise through events in which a gene or genes are mistakenly duplicated during cell division. Unlike their parent genes (which are subject to selection pressure to maintain function), these gene copies do not need to preserve their sequences and may evolve at a relatively faster rate.
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Occasionally these regions can be adapted to take on new roles within the organism, becoming novel genes...
Cooperative 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...
Duplication of Chromatin Structure
The process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
The basic unit of the chromatin is the nucleosome, consisting of DNA wrapped around octameric histone proteins and short stretches of linker DNA separating individual nucleosomes. The histone proteins within the nucleosome have their...
Single-Strand DNA Binding Proteins
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...
The DNA Helix
Deoxyribonucleic acid, or DNA, is the genetic material responsible for passing traits from generation to generation in all organisms and most viruses. DNA is composed of two strands of nucleotides that wind around each other to form a spring-like structure called a double helix. However, the double helix is not perfectly symmetrical. Instead, there are regularly occurring grooves in the structure. The major groove occurs where the sugar-phosphate backbones are relatively far apart. This space...


