Biological functions that depend upon the bridge helix of RNA polymerase
依赖于 RNA 聚合酶桥螺旋的生物学功能
基本信息
- 批准号:BB/J002828/1
- 负责人:
- 金额:$ 50.17万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2011
- 资助国家:英国
- 起止时间:2011 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Cells in all living organisms work through the concerted actions of tiny machines that carry out major transformations to allow growth and adaption. These tiny machines using the building blocks of life as their substrates, and form valuable materials from them, but also dismantle such materials when times so require.Ultimately, the DNA in cells is the blue print for these tiny machines, and will set how the machines interact with each other, the cells components, and importantly DNA itself. The genetic information in DNA must be accessed to allow cells to grow, adapt and to differentiate. Access is granted by the regulated activity of the RNA polymerase enzyme, a large and complex protein which copies DNA into an RNA template from which proteins are then produced. In this proposal we seek to work out how one conserved structural feature of RNA polymerase communicates with other conserved structural features of RNA polymerase to achieve 'full' functionality (in terms of accessing the information in DNA).The coupling interactions we plan to study-which can be thought of as being like the direct coupling of mechanical parts that allow engines to work and deliver force- are proposed to be required for the full functionality of RNA polymerase, but to date are not proven to exist. Specifically we will examine (i) interactions between the so called switch regions of RNA polymerase and one end of a long helical feature called the bridge helix; (ii) determine why altered forms of the bridge helix (eg the E. coli F773A mutant) works well in vitro but fails to support in vivo growth of cells;(iii) determine where points of bending in the alpha helical bridge helix are and what they are important for and (iv) look at how an RNA polymerase associated protein that directs it to specific DNA sequences (termed the promoter-specific sigma factor) can impact upon the functioning of the bridge helix. Gaining insights into how bacterial RNA polymerase works has important implications for the understanding of the functioning of all multi-subunit RNA polymerases, as well as in providing knowledge to help in the design of new anti-microbials that target the transcription apparatus.Our final aim is closely related to this longer term goal, since it seems that the feature of the RNA polymerase we wish to study is very flexible and may need to kink to work, indicating it might be captured in an unfavourable configuration by bespoke RNA polymerase-binding chemicals that would then act as inhibitors of its activity. We believe that through knowing how the RNA polymerase enzyme functions we can contribute to new strategies to mange infections and disease, as well as found new ways to improve biotechnological applications, such as protein and bio-chemicals productions.
所有生物体中的细胞都是通过微小机器的协调行动来工作的,这些机器进行重大转变以允许生长和适应。这些微小的机器以生命的基石为基质,并从中形成有价值的材料,但也会在需要时拆除这些材料。最终,细胞中的DNA是这些微小机器的蓝图,并将设定机器如何相互作用,细胞成分,以及重要的DNA本身。DNA中的遗传信息必须被访问,以允许细胞生长,适应和分化。通过RNA聚合酶的受调节活性来授予访问权限,RNA聚合酶是一种大而复杂的蛋白质,它将DNA复制到RNA模板中,然后从RNA模板产生蛋白质。在这个提议中,我们试图找出RNA聚合酶的一个保守结构特征如何与RNA聚合酶的其他保守结构特征进行通信,以实现“完整”功能我们计划研究的耦合相互作用-可以被认为是像机械部件的直接耦合,使发动机能够工作并传递力-被认为是RNA聚合酶的全部功能所必需的,但迄今为止尚未证明存在。具体来说,我们将研究(i)RNA聚合酶的所谓开关区域与称为桥螺旋的长螺旋特征的一端之间的相互作用;(ii)确定为什么桥螺旋的改变形式(例如E. coli F773 A突变体)在体外效果良好,但无法支持细胞的体内生长;(iii)确定α螺旋桥螺旋中的弯曲点在哪里以及它们对什么很重要;(iv)研究RNA聚合酶相关蛋白如何将其引导到特定DNA序列(称为启动子特异性西格玛因子)可以影响桥螺旋的功能。深入了解细菌RNA聚合酶如何工作,对于理解所有多亚基RNA聚合酶的功能具有重要意义,并提供知识以帮助设计靶向转录装置的新抗菌剂。我们的最终目标与这一长期目标密切相关,由于我们希望研究的RNA聚合酶的特征似乎非常灵活,可能需要扭结才能工作,这表明它可能被定制的RNA聚合酶结合化学物质以不利的构型捕获,然后作为其活性的抑制剂。我们相信,通过了解RNA聚合酶的功能,我们可以为管理感染和疾病的新策略做出贡献,并找到改进生物技术应用的新方法,例如蛋白质和生物化学品生产。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mutations in RNA Polymerase Bridge Helix and Switch Regions Affect Active-Site Networks and Transcript-Assisted Hydrolysis.
- DOI:10.1016/j.jmb.2015.09.005
- 发表时间:2015-11-06
- 期刊:
- 影响因子:5.6
- 作者:Zhang N;Schäfer J;Sharma A;Rayner L;Zhang X;Tuma R;Stockley P;Buck M
- 通讯作者:Buck M
Transcription Regulation and Membrane Stress Management in Enterobacterial Pathogens.
- DOI:10.1007/978-3-319-32189-9_13
- 发表时间:2016-05
- 期刊:
- 影响因子:0
- 作者:Nan Zhang;G. Jovanovic;C. McDonald;O. Ces;Xiaodong Zhang;M. Buck
- 通讯作者:Nan Zhang;G. Jovanovic;C. McDonald;O. Ces;Xiaodong Zhang;M. Buck
Activity map of the Escherichia coli RNA polymerase bridge helix.
- DOI:10.1074/jbc.m110.212902
- 发表时间:2011-04-22
- 期刊:
- 影响因子:0
- 作者:Jovanovic M;Burrows PC;Bose D;Cámara B;Wiesler S;Zhang X;Wigneshweraraj S;Weinzierl RO;Buck M
- 通讯作者:Buck M
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:
- 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
Domain movements of the enhancer-dependent sigma factor drive DNA delivery into the RNA polymerase active site: insights from single molecule studies.
- DOI:10.1093/nar/gku146
- 发表时间:2014-04
- 期刊:
- 影响因子:14.9
- 作者:Sharma A;Leach RN;Gell C;Zhang N;Burrows PC;Shepherd DA;Wigneshweraraj S;Smith DA;Zhang X;Buck M;Stockley PG;Tuma R
- 通讯作者:Tuma R
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Martin Buck其他文献
Regulation of the nitrogen fixation genes inKlebsiella pneumoniae: Implications for genetic manipulation
肺炎克雷伯菌固氮基因的调控:对基因操作的影响
- DOI:
- 发表时间:
1986 - 期刊:
- 影响因子:4.9
- 作者:
Ray Dixon;Martin Buck;Martin Drummond;T. Hawkes;Haseena Khan;S. MacFarlane;Mike Merrick;John Postgate - 通讯作者:
John Postgate
Nucleotide-dependent interactions between a fork junction-RNA polymerase complex and an AAA+ transcriptional activator protein.
叉连接-RNA 聚合酶复合物和 AAA 转录激活蛋白之间的核苷酸依赖性相互作用。
- DOI:
- 发表时间:
2004 - 期刊:
- 影响因子:14.9
- 作者:
W. Cannon;J. Schumacher;Martin Buck - 通讯作者:
Martin Buck
Conformational Changes of <em>Escherichia coli</em> σ<sup>54</sup>-RNA-Polymerase upon Closed–Promoter Complex Formation
- DOI:
10.1016/j.jmb.2005.09.057 - 发表时间:
2005-11-25 - 期刊:
- 影响因子:
- 作者:
Pampa Ray;Richard J. Hall;Robert D. Finn;Shaoxia Chen;Ardan Patwardhan;Martin Buck;Marin van Heel - 通讯作者:
Marin van Heel
Regulatory sequences in sigma 54 localise near the start of DNA melting.
西格玛 54 中的调控序列位于 DNA 解链起点附近。
- DOI:
10.1006/jmbi.2000.4393 - 发表时间:
2001 - 期刊:
- 影响因子:5.6
- 作者:
S. Wigneshweraraj;M. Chaney;Akira Ishihama;Martin Buck - 通讯作者:
Martin Buck
Sequences within the DNA Cross-linking Patch of ς<sup>54</sup>Involved in Promoter Recognition, ς Isomerization, and Open Complex Formation
- DOI:
10.1074/jbc.m002253200 - 发表时间:
2000-07-21 - 期刊:
- 影响因子:
- 作者:
Matthew Chaney;Melinda Pitt;Martin Buck - 通讯作者:
Martin Buck
Martin Buck的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Martin Buck', 18)}}的其他基金
Absolute quantification of SARS-CoV-2 proteins and their human targets for informing drug strategies and accelerating vaccine development
SARS-CoV-2 蛋白及其人类靶标的绝对定量,为药物策略提供信息并加速疫苗开发
- 批准号:
BB/V013866/1 - 财政年份:2020
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
Engineering the bacterium Rhodopseudomonas palustris as a platform for electrosynthetic bioproduction
将沼泽红假单胞菌工程化为电合成生物生产平台
- 批准号:
BB/R009171/1 - 财政年份:2018
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
Managing the Nitrogen economy of bacteria
管理细菌的氮经济
- 批准号:
BB/N003608/1 - 财政年份:2016
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
Role of RNA repair in the tolerance of bacteria to antibiotics.
RNA 修复在细菌对抗生素耐受性中的作用。
- 批准号:
MR/M017672/1 - 财政年份:2015
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
RNA FISH to determine bacterial RNA polymerase functionalities required for sigma factor specific escape from antibiotic action
RNA FISH 用于确定细菌 RNA 聚合酶的功能,该功能是 Sigma 因子特异性逃避抗生素作用所需的
- 批准号:
BB/L027135/1 - 财政年份:2014
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
Design and construction of electrogenic cell-based biosensors for pathogens and toxins
病原体和毒素的基于细胞的生电生物传感器的设计和构建
- 批准号:
BB/K016288/1 - 财政年份:2013
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
Determining bacterial RNA polymerase functionalities required for sigma factor specific escape from antibiotic action.
确定细菌 RNA 聚合酶功能所需的西格玛因子特异性逃避抗生素作用。
- 批准号:
BB/J00717X/1 - 财政年份:2012
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
Mapping combinatorial stress responses in bacteria using chimeric proteins and probabilistic modelling
使用嵌合蛋白和概率模型绘制细菌的组合应激反应
- 批准号:
BB/G020434/1 - 财政年份:2009
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
Geometric requirements for gene activation
基因激活的几何要求
- 批准号:
BB/G001278/1 - 财政年份:2008
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
The RNA polymerase bridge helix and domain communication
RNA聚合酶桥螺旋和结构域通讯
- 批准号:
BB/E000975/1 - 财政年份:2006
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
相似国自然基金
数学物理中精确可解模型的代数方法
- 批准号:11771015
- 批准年份:2017
- 资助金额:48.0 万元
- 项目类别:面上项目
相似海外基金
Cosmological hydrodynamical simulations with calibrated non-universal initial mass functions
使用校准的非通用初始质量函数进行宇宙流体动力学模拟
- 批准号:
2903298 - 财政年份:2027
- 资助金额:
$ 50.17万 - 项目类别:
Studentship
New substrates and functions for the DYRK protein kinases
DYRK 蛋白激酶的新底物和功能
- 批准号:
2894877 - 财政年份:2024
- 资助金额:
$ 50.17万 - 项目类别:
Studentship
Adaptive Artificial Receptors for Biomimetic Functions
仿生功能的自适应人工受体
- 批准号:
MR/X023303/1 - 财政年份:2024
- 资助金额:
$ 50.17万 - 项目类别:
Fellowship
Immunoregulatory functions of appetite controlling brain circuits
食欲控制脑回路的免疫调节功能
- 批准号:
BB/Y005694/1 - 财政年份:2024
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
New substrates and functions for the DYRK protein kinases
DYRK 蛋白激酶的新底物和功能
- 批准号:
BB/Y512527/1 - 财政年份:2024
- 资助金额:
$ 50.17万 - 项目类别:
Training Grant
Norway. Neuropeptide origins; study of neuropeptide functions in choanoflagellates
挪威。
- 批准号:
BB/X018512/1 - 财政年份:2024
- 资助金额:
$ 50.17万 - 项目类别:
Research Grant
NSF PRFB FY 2023: Impact of Environment-Seagrass-Microbe Interactions on Seagrass Stress Response and Ecosystem Functions
NSF PRFB 2023 财年:环境-海草-微生物相互作用对海草应激反应和生态系统功能的影响
- 批准号:
2305691 - 财政年份:2024
- 资助金额:
$ 50.17万 - 项目类别:
Fellowship Award
CAREER: Green Functions as a Service: Towards Sustainable and Efficient Distributed Computing Infrastructure
职业:绿色功能即服务:迈向可持续、高效的分布式计算基础设施
- 批准号:
2340722 - 财政年份:2024
- 资助金额:
$ 50.17万 - 项目类别:
Continuing Grant
Theory and algorithms for a new class of computationally amenable nonconvex functions
一类新的可计算非凸函数的理论和算法
- 批准号:
2416250 - 财政年份:2024
- 资助金额:
$ 50.17万 - 项目类别:
Standard Grant
Conference: Modular forms, L-functions, and Eigenvarieties
会议:模形式、L 函数和特征变量
- 批准号:
2401152 - 财政年份:2024
- 资助金额:
$ 50.17万 - 项目类别:
Standard Grant