Dual functionality of twin-arginine signal peptides

双精氨酸信号肽的双重功能

• 批准号: BB/D018986/1
• 负责人: Frank Sargent
• 金额: $ 30.94万
• 依托单位: University of Dundee
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD018986%2F1
• 关键词: Dual; functionality; twin; arginine; signal

Prokaryotes are the simplest truly living organisms known to man. They include the single-celled bacteria and their cousins the archaea, probably the closest surviving examples of the earliest cellular life-forms that ever existed. Many of these organisms can live and grow without oxygen, and instead utilise other chemicals from the environment to generate energy for life and nitrogen-rich chemicals such as nitrates are very commonly used as a replacement across the whole spectrum of prokaryotes. To get energy from nitrate prokaryotes contain special proteins or enzymes, many of which are made-up of lots of different parts, or subunits, which in themselves often contain metal and sulphur atoms. In addition, these enzymes are often found 'outside' on the surface of the cell. How these enzymes get out the cell, and how they are fully assembled with all their metals and subunits attached before that, is the thrust of this research project. Most enzymes that are destined to be located outside the cell are identifiable by the presence of a special 'signal' on them. We have found this signal, which is also made of protein, has two jobs in the cell. First, it helps to assemble the subunits and metals, then second, it helps to locate the finished enzyme outside the cell. We want to study these functions in isolation, without interference from the other one, in order to understand them fully and in detail. We will then look again at the complete system and applying our new knowledge to understand how the two functions work together in harmony. Once we learn in detail how these processes work we may be able to make it work 'better' so that biotechnology companies can use it to make useful everyday products. Or we may be able to learn how design a new antibiotic to stop this system working without harming the environment - some deadly bacteria that cannot perform these tasks are no longer dangerous.

原核生物是人类所知的最简单的真正的生物体，包括单细胞细菌和它们的近亲古生菌，它们可能是最早的细胞生命形式中最接近的幸存例子。这些生物中的许多可以在没有氧气的情况下生存和生长，而是利用环境中的其他化学物质为生命产生能量，而富含氮的化学物质如硝酸盐通常被用作整个原核生物谱的替代品。为了从硝酸盐中获得能量，原核生物含有特殊的蛋白质或酶，其中许多是由许多不同的部分或亚基组成的，它们本身通常含有金属和硫原子。此外，这些酶通常在细胞表面的“外部”发现。这些酶如何离开细胞，以及它们如何与所有金属和亚基完全组装在一起，这是这个研究项目的重点。大多数注定位于细胞外的酶都可以通过其上存在的特殊“信号”来识别。我们已经发现这种信号也是由蛋白质组成的，在细胞中有两种作用。首先，它有助于组装亚基和金属，其次，它有助于将成品酶定位在细胞外。我们希望孤立地研究这些功能，而不受其他功能的干扰，以便充分和详细地了解它们。然后，我们将再次审视整个系统，并应用我们的新知识来理解这两个功能如何和谐地协同工作。一旦我们详细了解了这些过程是如何工作的，我们就可以让它“更好地”工作，这样生物技术公司就可以用它来制造有用的日常产品。或者我们可以学习如何设计一种新的抗生素来阻止这个系统的工作而不损害环境-一些无法执行这些任务的致命细菌不再危险。

项目成果

Biosynthesis of selenate reductase in Salmonella enterica: critical roles for the signal peptide and DmsD.

• DOI: 10.1099/mic.0.000381
• 发表时间: 2016-12
• 期刊: Microbiology (Reading, England)
• 作者: Connelly KRS;Stevenson C;Kneuper H;Sargent F
• 通讯作者: Sargent F

Conserved signal peptide recognition systems across the prokaryotic domains.

• DOI: 10.1021/bi201852d
• 发表时间: 2012-02-28
• 期刊: BIOCHEMISTRY
• 影响因子: 2.9
• 作者: Coulthurst, Sarah J.;Dawson, Alice;Hunter, William N.;Sargent, Frank
• 通讯作者: Sargent, Frank

Signal peptide etiquette during assembly of a complex respiratory enzyme.

复杂呼吸酶组装过程中的信号肽礼仪。

• DOI: 10.1111/mmi.12373
• 发表时间: 2013
• 期刊: Molecular microbiology
• 影响因子: 3.6
• 作者: James MJ