Architecture of the bacterial divisome.
细菌分裂体的结构。
基本信息
- 批准号:BB/M001180/1
- 负责人:
- 金额:$ 54.07万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2015
- 资助国家:英国
- 起止时间:2015 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
All cell types need to grow and to divide in order to survive. Bacteria, one of the most primitive and ancient of all life forms, divide by a relatively simple mechanism, but nonetheless in a process that is tightly controlled and co-ordinated. The key steps include the replication of the cell's DNA, so that each copy of the cell has an identical copy of the genome, the blueprint of life. The two copies of the genome then have to be separated so that they are not entangled when the mother and daughter cells finally separate to become discrete entities, each with an identical copy of the genome. The division process normally takes place at the centre of the dividing cell and a molecular machine called the Z-ring acts as a belt, constricting tighter and tighter across the middle of the cell until it closes completely, pinching off the daughter from the mother cell. Imagine a small balloon, grasped between thumb and forefinger. As the forefinger bends like a pincer against the thumb, air is squeezed into the two halves of the balloon. When there is no gap between forefinger and thumb, each of the balloon halves, one in the palm of your hand and one above your fingers, are the same volume. As the Z-ring tightens, a protective layer called peptidoglycan, made of strands of carbohydrate cross-linked by short peptide fragments, has to be made afresh and deposited on the surface of the cell. This action must be co-ordinated with all aspects of the division process, otherwise the cell membrane is left uncovered and is prone to rupture, causing death of the cell.This proposal concerns how the regulation of the closure of the Z-ring is co-ordinated with peptidoglycan synthesis, and the precise role played by a key protein known as EzrA. These activities are co-ordinated by a multi-protein assembly called the divisome, which links the Z-ring to peptidoglycan synthesis, but in a manner that is not yet understood. We have recently solved the structure of EzrA, which is surprisingly similar to a class of proteins called spectrins that, in animals, are used to link membrane-embedded proteins to the cytoskeleton. The cytoskeleton is a shape-defining structure found on the inside face of the cytoplasmic membrane in many cell types, including bacteria, comprising different proteins including actin and tubulin. The bacterial cytoskeleton also comprises actin and tubulin-type proteins, the latter of which is the key component of the contractile Z-ring. EzrA is therefore a structural and functional homologue of spectrin, as it acts to link the cytoskeleton to membrane-embedded proteins that synthesise peptidoglycan, and other membrane-embedded cell division regulators. In this proposal we will ascertain the molecular mechanisms used by EzrA to interact with the cytoskeleton, other members of the divisome, including the enzymes that generate peptidoglycan, and key regulators of cell division. The research program will enable for detailed comparisons to be made between the cytoskeletons of bacteria and of animals, which is currently focussed on one or two proteins. A greater understanding of the relationships and the differences between the two cytoskeletons will also provide a greater understanding of the evolution of multicellular life forms from their simpler, single-celled predecessors.
所有类型的细胞都需要生长和分裂才能生存。细菌是所有生命形式中最原始和最古老的一种,其分裂机制相对简单,但其过程受到严格控制和协调。关键步骤包括细胞DNA的复制,这样每个细胞的拷贝都有一个相同的基因组拷贝,基因组是生命的蓝图。然后,基因组的两个拷贝必须被分离,以便当母细胞和子细胞最终分离成为离散实体时,它们不会纠缠在一起,每个实体都有一个相同的基因组拷贝。分裂过程通常发生在分裂细胞的中心,一种称为Z环的分子机器就像一条带子,在细胞的中间越来越紧,直到它完全关闭,从母细胞中夹出子细胞。想象一个小气球,用拇指和食指抓住。当食指像钳子一样弯曲抵住拇指时,空气被挤压到气球的两半中。当食指和拇指之间没有间隙时,每个气球的一半,一个在你的手掌上,一个在你的手指上方,是相同的体积。当Z环收紧时,一层称为肽聚糖的保护层,由短肽片段交联的碳水化合物链组成,必须重新形成并沉积在细胞表面。这一过程必须与细胞分裂过程的各个方面相协调,否则细胞膜将暴露在外,容易破裂,导致细胞死亡。这一提议涉及Z环的闭合调节如何与肽聚糖合成相协调,以及一种称为EzrA的关键蛋白质所起的确切作用。这些活动是由一个多蛋白质组装称为divisome协调,它连接Z环的肽聚糖合成,但在一种方式,目前还不清楚。我们最近已经解决了EzrA的结构,它与一类称为血影蛋白的蛋白质惊人地相似,在动物中,血影蛋白用于将膜包埋蛋白质连接到细胞骨架。细胞骨架是在包括细菌在内的许多细胞类型的细胞质膜的内表面上发现的形状限定结构,其包含不同的蛋白质,包括肌动蛋白和微管蛋白。细菌细胞骨架还包括肌动蛋白和微管蛋白型蛋白,后者是收缩Z环的关键组成部分。因此,EzrA是血影蛋白的结构和功能同源物,因为它的作用是将细胞骨架连接到合成肽聚糖的膜包埋蛋白和其他膜包埋细胞分裂调节剂。在这项提议中,我们将确定EzrA与细胞骨架,分裂体的其他成员,包括产生肽聚糖的酶,以及细胞分裂的关键调节因子相互作用的分子机制。该研究计划将能够在细菌和动物的细胞骨架之间进行详细的比较,目前主要集中在一两种蛋白质上。更好地理解两种细胞骨架之间的关系和差异,也将更好地理解多细胞生命形式从其简单的单细胞前辈进化而来。
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)
EzrA: a spectrin-like scaffold in the bacterial cell division machinery.
- DOI:10.15698/mic2015.02.187
- 发表时间:2015-01-15
- 期刊:
- 影响因子:0
- 作者:Cleverley R;Lewis R
- 通讯作者:Lewis R
The cell cycle regulator GpsB functions as cytosolic adaptor for multiple cell wall enzymes
- DOI:10.1038/s41467-018-08056-2
- 发表时间:2019-01-16
- 期刊:
- 影响因子:16.6
- 作者:Cleverley, Robert M.;Rutter, Zoe J.;Lewis, Richard J.
- 通讯作者:Lewis, Richard J.
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Richard Lewis其他文献
Exploring information retrieval, semantic technologies and workflows for music scholarship: the Transforming Musicology project
探索音乐学术的信息检索、语义技术和工作流程:转变音乐学项目
- DOI:
- 发表时间:
2015 - 期刊:
- 影响因子:0
- 作者:
Richard Lewis;T. Crawford;David Lewis - 通讯作者:
David Lewis
The C@merata task at MediaEval 2016: Natural Language Queries Derived from Exam Papers, Articles and Other Sources against Classical Music Scores in MusicXML
MediaEval 2016 上的 C@merata 任务:针对 MusicXML 中的古典音乐乐谱从试卷、文章和其他来源导出的自然语言查询
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:0
- 作者:
R. Sutcliffe;Tom Collins;E. Hovy;Richard Lewis;C. Fox;Deane L. Root - 通讯作者:
Deane L. Root
Parental Occupation and the Gender Math Gap: Examining the Social Reproduction of Academic Advantage among Elementary and Middle School Students
父母职业与性别数学差距:审视中小学生学业优势的社会再生产
- DOI:
10.3390/socsci7010006 - 发表时间:
2017 - 期刊:
- 影响因子:0
- 作者:
Monica Bowden;J. Bartkowski;Xiaohe Xu;Richard Lewis - 通讯作者:
Richard Lewis
NP36 - Using the Child as Change Agent for Preventing Childhood Obesity in Rural Georgia: Home Environment Results
- DOI:
10.1016/j.jneb.2018.04.272 - 发表时间:
2018-07-01 - 期刊:
- 影响因子:
- 作者:
Marsha Davis;Courtney Brown;Andrea Scarrow;Frances McCarty;Richard Christiana;Richard Lewis;Rebecca Mullis - 通讯作者:
Rebecca Mullis
Artificial intelligence in chemistry and drug design
- DOI:
10.1007/s10822-020-00317-x - 发表时间:
2020-05-29 - 期刊:
- 影响因子:3.100
- 作者:
Nathan Brown;Peter Ertl;Richard Lewis;Torsten Luksch;Daniel Reker;Nadine Schneider - 通讯作者:
Nadine Schneider
Richard Lewis的其他文献
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{{ truncateString('Richard Lewis', 18)}}的其他基金
NSF-SSRC: Reducing Vaccine Hesitancy Through Interactive Decision Aids
NSF-SSRC:通过交互式决策辅助工具减少疫苗犹豫
- 批准号:
2241963 - 财政年份:2023
- 资助金额:
$ 54.07万 - 项目类别:
Continuing Grant
Is the GpsB:PBP1 interaction an Achilles' heel for Gram-positive pathogens?
GpsB:PBP1 相互作用是革兰氏阳性病原体的致命弱点吗?
- 批准号:
BB/R012520/1 - 财政年份:2018
- 资助金额:
$ 54.07万 - 项目类别:
Research Grant
Phosphotransferases in bacterial cell wall biosynthesis
细菌细胞壁生物合成中的磷酸转移酶
- 批准号:
BB/J015016/1 - 财政年份:2012
- 资助金额:
$ 54.07万 - 项目类别:
Research Grant
Language Processing as Boundedly Optimal Control of Memory, Perception, and Action
语言处理作为记忆、感知和行动的有限最优控制
- 批准号:
1152819 - 财政年份:2012
- 资助金额:
$ 54.07万 - 项目类别:
Continuing Grant
Modelling carbon core metabolism in Bacillus subtilis - exploring the contribution of protein complexes in core carbon and nitrogen metabolism
模拟枯草芽孢杆菌的碳核心代谢 - 探索蛋白质复合物在核心碳和氮代谢中的贡献
- 批准号:
BB/I004572/1 - 财政年份:2010
- 资助金额:
$ 54.07万 - 项目类别:
Research Grant
Functional studies of the stressosome
应激体的功能研究
- 批准号:
BB/F001533/1 - 财政年份:2008
- 资助金额:
$ 54.07万 - 项目类别:
Research Grant
The activation mechanism of the Bacillus subtilis stressosome signalling hub
枯草芽孢杆菌应激体信号中枢的激活机制
- 批准号:
BB/G001553/1 - 财政年份:2008
- 资助金额:
$ 54.07万 - 项目类别:
Research Grant
Structural analysis of the interaction networks
交互网络的结构分析
- 批准号:
BB/F003404/1 - 财政年份:2007
- 资助金额:
$ 54.07万 - 项目类别:
Research Grant
RUI: Establishment of a high-density event-related potential laboratory at an undergraduate college for the study of cognitive neuroscience
RUI:在本科院校建立高密度事件相关电位实验室,进行认知神经科学研究
- 批准号:
0116836 - 财政年份:2001
- 资助金额:
$ 54.07万 - 项目类别:
Standard Grant
Laboratory Equipment to Improve Undergraduate Instruction inPhysiological Psychology
改善生理心理学本科教学的实验室设备
- 批准号:
8750744 - 财政年份:1987
- 资助金额:
$ 54.07万 - 项目类别:
Standard Grant
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中国棉铃虫核多角体病毒基因组库和分子进化
- 批准号:30540076
- 批准年份:2005
- 资助金额:8.0 万元
- 项目类别:专项基金项目
细菌脂蛋白(BLP)诱导LPS交叉耐受的分子机理研究
- 批准号:30471791
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- 资助金额:20.0 万元
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相似海外基金
robing the structure and stability of the bacterial divisome
改变细菌分裂体的结构和稳定性
- 批准号:
571796-2022 - 财政年份:2022
- 资助金额:
$ 54.07万 - 项目类别:
University Undergraduate Student Research Awards
Integrated analysis of the bacterial divisome using multiple probes
使用多个探针对细菌分裂体进行综合分析
- 批准号:
18K06094 - 财政年份:2018
- 资助金额:
$ 54.07万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Investigating the molecular architecture of the multicomponent Z-ring that constitutes the divisome structure involved in bacterial cell division.
研究构成参与细菌细胞分裂的分裂体结构的多组分 Z 环的分子结构。
- 批准号:
487455-2016 - 财政年份:2018
- 资助金额:
$ 54.07万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Investigating the molecular architecture of the multicomponent Z-ring that constitutes the divisome structure involved in bacterial cell division.
研究构成参与细菌细胞分裂的分裂体结构的多组分 Z 环的分子结构。
- 批准号:
487455-2016 - 财政年份:2017
- 资助金额:
$ 54.07万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Investigating the molecular architecture of the multicomponent Z-ring that constitutes the divisome structure involved in bacterial cell division.
研究构成参与细菌细胞分裂的分裂体结构的多组分 Z 环的分子结构。
- 批准号:
487455-2016 - 财政年份:2016
- 资助金额:
$ 54.07万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Doctoral
Probing the structure and stability of the bacterial divisome
探究细菌分裂体的结构和稳定性
- 批准号:
483533-2015 - 财政年份:2015
- 资助金额:
$ 54.07万 - 项目类别:
University Undergraduate Student Research Awards
Probing the structure and stability of the bacterial divisome
探究细菌分裂体的结构和稳定性
- 批准号:
466928-2014 - 财政年份:2014
- 资助金额:
$ 54.07万 - 项目类别:
University Undergraduate Student Research Awards
Structural study of transmembrane interactions in the bacterial divisome
细菌分裂体跨膜相互作用的结构研究
- 批准号:
9188131 - 财政年份:2013
- 资助金额:
$ 54.07万 - 项目类别:
Structural study of transmembrane interactions in the bacterial divisome
细菌分裂体跨膜相互作用的结构研究
- 批准号:
9050070 - 财政年份:2013
- 资助金额:
$ 54.07万 - 项目类别:
Structural study of transmembrane interactions in the bacterial divisome
细菌分裂体跨膜相互作用的结构研究
- 批准号:
8724521 - 财政年份:2013
- 资助金额:
$ 54.07万 - 项目类别: