A biochemical and biophysical analysis of a ubiquitous protein translocation apparatus

普遍存在的蛋白质易位装置的生化和生物物理分析

• 批准号: BB/F002343/1
• 负责人: Ian Collinson
• 金额: $ 42.25万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2008
• 资助国家: 英国
• 起止时间: 2008 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF002343%2F1
• 关键词: biochemical; biophysical; analysis; ubiquitous; protein

An ancient and essential development for life on Earth has been the evolution of a thin film of lipids that surround and form each cell. These membranes provide a barrier to water and hydrophilic solutes. They serve to isolate biological reactions from the outside, and offer the potential to separate charge and to communicate & aggregate with one another to form complex structures. More complicated cells also contain internal membrane structures that provide a further division for chemical reactions and generation of electric potentials. These events facilitated the ability to harness energy and to develop and maintain the complex structures and biochemistry of the cell. The necessary exchange of materials across lipid membranes between the outside and different compartments gives rise to a transport problem for small and large molecules alike. Proteins are large polymers of amino acids made according to the genetic code of each respective gene in the cell cytosol. In order to perform their specific roles many of them need to be delivered to alternative locations. This requires that they pass either across or into a specific membrane. This proposal aims to learn more about this important process using the bacterial cell membrane as a model system. The apparatus responsible for protein movement across membranes has been purified. Once prepared, various parts will then be labelled with chemical reagents that are able to report on their environment by the way that they interact with light. These probes will characterise the movements that the components make as they transport proteins across the membrane, which will aid our understanding of this reaction. New findings in this area will have implications in the understanding of protein secretion, cell biogenesis and development. Moreover, they will also help us understand other molecular machines and more general processes such as membrane transport. This information might be also exploited toward the development novel antibiotics.

地球上生命的一个古老而重要的发展是围绕和形成每个细胞的一层薄薄的脂膜的进化。这些膜对水和亲水性溶质具有阻隔作用。它们用于将生物反应与外界隔离，并提供分离电荷以及相互交流和聚集形成复杂结构的可能性。更复杂的细胞还包含内部膜结构，这些结构为化学反应和产生电位提供了进一步的划分。这些事件促进了利用能量以及发展和维持细胞的复杂结构和生物化学的能力。脂膜外部和不同隔室之间必要的物质交换引起了小分子和大分子的运输问题。蛋白质是根据细胞质中每个基因的遗传密码而形成的氨基酸的大聚合物。为了履行他们的具体职责，他们中的许多人需要被送到其他地点。这需要它们穿过或进入特定的膜。这项建议旨在利用细菌细胞膜作为模型系统来更多地了解这一重要过程。负责蛋白质跨膜移动的装置已经被提纯。一旦准备好，各个部分将被贴上化学试剂的标签，这些试剂能够通过它们与光相互作用的方式来报告它们所处的环境。这些探针将表征这些成分在跨膜运输蛋白质时所做的运动，这将有助于我们对这一反应的理解。这一领域的新发现将对理解蛋白质分泌、细胞生物发生和发育具有重要意义。此外，它们还将帮助我们了解其他分子机器和更一般的过程，如膜运输。这一信息也可能被用于开发新型抗生素。

项目成果

The oligomeric state and arrangement of the active bacterial translocon.

• DOI: 10.1074/jbc.m110.175638
• 发表时间: 2011-02-11
• 期刊: The Journal of biological chemistry
• 作者: Deville K;Gold VA;Robson A;Whitehouse S;Sessions RB;Baldwin SA;Radford SE;Collinson I
• 通讯作者: Collinson I

Structure of the SecY complex unlocked by a preprotein mimic.

• DOI: 10.1016/j.celrep.2011.11.003
• 发表时间: 2012-01-26
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Hizlan D;Robson A;Whitehouse S;Gold VA;Vonck J;Mills D;Kühlbrandt W;Collinson I
• 通讯作者: Collinson I