Mechanism of a nucleotide dependent transcription activation process

核苷酸依赖性转录激活过程的机制

• 批准号: BB/H012249/1
• 负责人: Xiaodong Zhang
• 金额: $ 116.96万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH012249%2F1
• 关键词: Mechanism; nucleotide; dependent; transcription; activation

The cells of every organism contain a chemical code within their DNA molecules that holds the information needed for making all the protein products required to make the cell grow and stay alive. The code is in the form of a linear sequence of nucleotide bases, the famous A,G, C & T. The order of these letters determines the subsequent linear order of amino acids of the cell's proteins, which ultimately determine its structure and function. Converting the nucleotide information into the encoded amino acid sequence is known as as gene expression. The first step in this process is one of the most important reactions inside cells and involves making an RNA copy - a transcript- of the DNA message. The enzymes involved in this process - RNA polymerases - must start the copying process at a defined point in DNA, known as the promoter. In cells, this process is tightly regulated and determines the pattern of genes being read and thus contributes to the precise execution of the cellular genetic program. We are studying the basic mechanisms that control the choice of start site and the controlled activation of the RNA polymerase from a passive DNA-binding protein into the active copying machine. In particular we are studying how the protein components of transcription machinery use the energy currency of the cell-a molecule called ATP-to function as small machines and to interconvert between different states. We would like to know the detailed features and the conformational changes in the transcription machinery during the initial steps - when the double stranded DNA is opened up in single strand forms and the template strand is delivered into the site of RNAP for synthesizing RNA.

每个生物体的细胞都在其DNA分子中包含一个化学密码，该密码包含使细胞生长和存活所需的所有蛋白质产物所需的信息。密码是以核苷酸碱基的线性序列的形式存在的，即著名的A、G、C和T。这些字母的顺序决定了细胞蛋白质氨基酸的线性顺序，最终决定了其结构和功能。将核苷酸信息转化为编码的氨基酸序列称为基因表达。这一过程的第一步是细胞内最重要的反应之一，涉及制造DNA信息的RNA拷贝-转录本。参与这一过程的酶-- RNA聚合酶--必须在DNA中一个被称为启动子的确定点启动复制过程。在细胞中，这一过程受到严格调节，并决定被读取基因的模式，从而有助于细胞遗传程序的精确执行。我们正在研究控制起始位点的选择和RNA聚合酶从被动的DNA结合蛋白到主动复制机器的受控激活的基本机制。特别是，我们正在研究转录机器的蛋白质成分如何使用细胞的能量货币-一种称为ATP的分子-作为小型机器发挥作用并在不同状态之间相互转换。我们想知道在最初的步骤中转录机制的详细特征和构象变化-当双链DNA以单链形式打开并且模板链被递送到RNAP的位点以合成RNA时。

项目成果

Structures of RNA Polymerase Closed and Intermediate Complexes Reveal Mechanisms of DNA Opening and Transcription Initiation.

• DOI: 10.1016/j.molcel.2017.05.010
• 发表时间: 2017-07-06
• 期刊: Molecular cell
• 影响因子: 16
• 作者: Glyde R;Ye F;Darbari VC;Zhang N;Buck M;Zhang X
• 通讯作者: Zhang X

The Dimeric Architecture of Checkpoint Kinases Mec1ATR and Tel1ATM Reveal a Common Structural Organization.

• DOI: 10.1074/jbc.m115.708263
• 发表时间: 2016-06-24
• 期刊: The Journal of biological chemistry
• 作者: Sawicka M;Wanrooij PH;Darbari VC;Tannous E;Hailemariam S;Bose D;Makarova AV;Burgers PM;Zhang X
• 通讯作者: Zhang X

Structures of Bacterial RNA Polymerase Complexes Reveal the Mechanism of DNA Loading and Transcription Initiation.

• DOI: 10.1016/j.molcel.2018.05.021
• 发表时间: 2018-06-21
• 期刊: Molecular cell
• 影响因子: 16
• 作者: Glyde R;Ye F;Jovanovic M;Kotta-Loizou I;Buck M;Zhang X
• 通讯作者: Zhang X

Molecular basis of nucleotide-dependent substrate engagement and remodeling by an AAA+ activator.

• DOI: 10.1093/nar/gku588
• 发表时间: 2014-08
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Darbari VC;Lawton E;Lu D;Burrows PC;Wiesler S;Joly N;Zhang N;Zhang X;Buck M
• 通讯作者: Buck M

Single-Particle Electron Microscopy Analysis of DNA Repair Complexes.

• DOI: 10.1016/bs.mie.2017.03.010
• 发表时间: 2017
• 期刊: Methods in enzymology
• 作者: M. Sawicka;R. Aramayo;Rafael Ayala;R. Glyde;Xiaodong Zhang