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Protein complex formation as a rationale for translation factories

蛋白质复合物的形成作为翻译工厂的基本原理

基本信息

批准号：
BB/V015109/1
负责人：
Mark Peter Ashe
金额：
$ 111.82万
依托单位：
University of Manchester
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2021
资助国家：
英国
起止时间：
2021 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FV015109%2F1
关键词：
Protein complex formation rationale translation

项目摘要

The information encoded in genes in living cells is decoded to produce chains of amino acids called proteins, which fold up to form functional and mature forms. The complement of mature proteins present in a cell dictate its identity, function and health. Proteins carry out most biological functions, catalyzing biochemical reactions as well as serving structural and regulatory roles. Most of these functions involve proteins acting in concert with other proteins, frequently in so-called molecular machines where different protein subunits come together to form complexes. This provides enormous flexibility and control, and cells devote large resources to making these complexes in all organisms from bacteria to man. When it goes wrong and protein complex assembly goes awry, this has wide ranging implications. For example, it is known that protein interaction surfaces are hot-spots for many human genetic disease-associated mutations.Estimates suggest that in yeast cells there are up to 60 million protein molecules per cell, whereas in a human cell this number rises to over 10 billion, and roughly half of these protein molecules in each system form part of protein complexes. The inherent complexity in producing so many molecular machines raises a key question: how do individual protein molecules within this protein sea find their correct, cognate partner(s) and form appropriate protein complexes? Given that each protein molecule is synthesized independently, using a template molecule, mRNA, it is not immediately obvious how cells solve this 'needle in a haystack' problem. However, recent evidence has shown a simple solution to this challenge is to ensure that the different proteins from the same complex are synthesized in the same defined subcellular location. This can be viewed as a factory, which specializes in making selected protein complexes. In order to achieve this, the cell factory model benefits from colocalizing the template mRNA molecules to the same locale. In this proposal, we will use the yeast cell due to its relative simplicity, and the range of reagents available to resolve a number of key questions linked to this model. We will determine how widespread this factory-associated assembly of protein complexes is, how the factories form and are regulated, and how important the factory-mediated assembly of protein complexes is for a cell's life.

活细胞中基因编码的信息被解码，产生称为蛋白质的氨基酸链，这些氨基酸链折叠形成功能性和成熟的形式。存在于细胞中的成熟蛋白质的补充决定了其身份，功能和健康。蛋白质执行大多数生物功能，催化生化反应以及担任结构和调节角色。这些功能中的大多数涉及与其他蛋白质协同作用的蛋白质，通常在所谓的分子机器中，不同的蛋白质亚基聚集在一起形成复合物。这提供了巨大的灵活性和控制能力，从细菌到人类，所有生物体的细胞都投入大量资源来制造这些复合物。当它出错时，蛋白质复合物组装出错，这具有广泛的影响。例如，已知蛋白质相互作用表面是许多人类遗传疾病相关突变的热点，估计在酵母细胞中每个细胞中有多达6000万个蛋白质分子，而在人类细胞中这个数字上升到超过100亿，每个系统中大约有一半的蛋白质分子形成蛋白质复合物的一部分。产生如此多的分子机器的固有复杂性提出了一个关键问题：蛋白质海洋中的单个蛋白质分子如何找到它们正确的同源伴侣并形成适当的蛋白质复合物？鉴于每个蛋白质分子都是独立合成的，使用模板分子mRNA，细胞如何解决这个“大海捞针”的问题并不明显。然而，最近的证据表明，解决这一挑战的一个简单方法是确保来自同一复合物的不同蛋白质在相同的亚细胞位置合成。这可以被视为一个工厂，专门制造选定的蛋白质复合物。为了实现这一点，细胞工厂模型受益于将模板mRNA分子共定位到相同的位置。在本提案中，我们将使用酵母细胞，因为它相对简单，以及可用于解决与此模型相关的许多关键问题的试剂范围。我们将确定这种工厂相关的蛋白质复合物组装有多普遍，工厂如何形成和调节，以及工厂介导的蛋白质复合物组装对细胞生命的重要性。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Integrated multi-omics reveals common properties underlying stress granule and P-body formation.

综合的多词揭示了应力颗粒和p体形成的共同特性。

DOI：
10.1080/15476286.2021.1976986
发表时间：
2021-11-12
期刊：
RNA biology
影响因子：
4.1
作者：
Kershaw CJ;Nelson MG;Lui J;Bates CP;Jennings MD;Hubbard SJ;Ashe MP;Grant CM
通讯作者：
Grant CM

Riboproteome remodeling during quiescence exit in Saccharomyces cerevisiae.

DOI：
10.1016/j.isci.2023.108727
发表时间：
2024-01-19
期刊：
ISCIENCE
影响因子：
5.8
作者：
Solari, Clara A.;Martinez, Maria Clara Ortola;Fernandez, Juan M.;Bates, Christian;Cueto, Gerardo;Valacco, Maria Pia;Morales-Polanco, Fabian;Moreno, Silvia;Rossi, Silvia;Ashe, Mark P.;Portela, Paula
通讯作者：
Portela, Paula

Targeting of Proteins for Translocation at the Endoplasmic Reticulum.

DOI：
10.3390/ijms23073773
发表时间：
2022-03-29
期刊：
International journal of molecular sciences
影响因子：
5.6
作者：
Pool MR
通讯作者：
Pool MR

Core Fermentation (CoFe) granules focus coordinated glycolytic mRNA localization and translation to fuel glucose fermentation.

核心发酵（COFE）颗粒聚焦的糖酵解mRNA定位和转化为燃料葡萄糖发酵。

DOI：
10.1016/j.isci.2021.102069
发表时间：
2021-02-19
期刊：
iScience
影响因子：
5.8
作者：
Morales-Polanco F;Bates C;Lui J;Casson J;Solari CA;Pizzinga M;Forte G;Griffin C;Garner KEL;Burt HE;Dixon HL;Hubbard S;Portela P;Ashe MP
通讯作者：
Ashe MP

Translation factor and RNA binding protein mRNA interactomes support broader RNA regulons for posttranscriptional control.

翻译因子和RNA结合蛋白mRNA相互作用组支持更广泛的RNA调节，用于转录后控制。

DOI：
10.1016/j.jbc.2023.105195
发表时间：
2023-10
期刊：
JOURNAL OF BIOLOGICAL CHEMISTRY
影响因子：
4.8
作者：
Kershaw, Christopher J.;Nelson, Michael G.;Castelli, Lydia M.;Jennings, Martin D.;Lui, Jennifer;Talavera, David;Grant, Chris M.;Pavitt, Graham D.;Hubbard, Simon J.;Ashe, Mark P.
通讯作者：
Ashe, Mark P.