Iron mobilisation in the bacterial cell

细菌细胞中的铁动员

• 批准号: BB/D002435/1
• 负责人: Simon C Andrews
• 金额: $ 26.79万
• 依托单位: University of Reading
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD002435%2F1
• 关键词: Iron; mobilisation; bacterial; cell

Nearly all organisms depend on iron for their existence. Iron is a key element for life because of its abundance in the earths crust and its useful chemical and physical properties - e.g. it is very good at transferring electrons, and activating oxygen for reaction with a range of substrates. Both of these are key processes in respiration - the means by which energy stored in foods is converted into a useable form - thus illustrating why organisms are dependent on this metal. Despite its abundance and useful properties, iron presents organisms with two problems. Firstly, ever since the oxygen levels in the earth's atmosphere began to increase, iron has been present largely in an oxidised and highly insoluble mineral form that is not readily available for utilisation by organisms. As a consequence, iron is often a limiting nutrient for growth and its availability can, for example, determine whether or not a bacterial pathogen can successfully colonise its host. Secondly, the chemistry that makes iron so useful means that it can also be highly toxic to the cell. To counter these problems, a whole range of smart mechanisms have evolved that enable organisms to scavenge iron from their environment, to stock pile it when it is found in excess of immediate requirements, and to maintain it within the cell in a non-toxic form. The latter two are achieved by iron-storage molecules that are found in all cell types from the simplest to the most complex. Iron-storage proteins belong to the 'ferritin super-family and have unusual structures consisting of 24 subunits arranged to form a large, spherical protein shell surrounding a central cavity where up to 4,500 iron atoms can be stored. Bacteria, which are the simplest of organisms, often contain two different types of ferritin: a ferritin (Ftn) which resembles closely the archetypal ferritins found in mammals, and a bacterioferritin (BFR) which are more distantly related heme-containing proteins, so far found only in bacteria. We and others have studied these iron-storage proteins in the model bacterium, E. coli, and so understand in some detail how their synthesis is controlled and how they are able to store large quantities of iron. In times of environmental iron deficiency, bacteria and other organisms mobilise their iron stores to compensate for the lack of external iron. However, very little is known about how iron is released from iron stores, either in bacteria or in more complex organisms such as mammals. We and others have identified a small electron transfer protein, Bfd, which we propose plays a key role in iron mobilisation from BFR. We now wish to test our hypothesis and to characterise, for the first time in any organism, the processes involved in iron mobilisation from iron-storage proteins. The research proposed here uniquely brings together our expertises in the physiology of iron metabolism (at Reading) and the biochemistry of iron-storage proteins (at UEA) in order to tackle this major remaining question of iron metabolism. Using a truly multi-disciplinary approach employing a wide range of genetic, biochemical and bioanalytical methods, we will study in detail iron mobilisation from BFR and Ftn in E. coli, and the role played by Bfd and other relevant factors in this process. We will also clarify the respective roles of BFR and Ftn in the iron-storage process (it is unclear why E. coli and other bacteria possess two such distinct iron-storage proteins) and seek to identify other cellular factors that interact with these proteins. This work will have a major impact on our understanding of how bacteria utilise previously stored iron for synthetic processes. Joint with BB/D001943/1.

几乎所有的生物都依赖铁元素生存。铁是生命的关键元素，因为它在地壳中含量丰富，而且具有有用的化学和物理性质——例如，它非常善于转移电子，并能激活氧与一系列底物发生反应。这两个都是呼吸的关键过程，呼吸是将储存在食物中的能量转化为可用形式的手段，因此说明了为什么生物体依赖这种金属。尽管铁元素丰富且具有有用的特性，但它给生物体带来了两个问题。首先，自从地球大气中的氧含量开始增加以来，铁主要以氧化和高度不溶的矿物形式存在，不容易被生物利用。因此，铁通常是一种限制生长的营养物质，例如，铁的可用性可以决定细菌病原体是否能成功地在其宿主上定植。其次，使铁如此有用的化学性质也意味着它对细胞有剧毒。为了解决这些问题，进化出了一系列智能机制，使生物体能够从环境中清除铁，在发现铁超过即时需求时储存铁，并以无毒的形式将其维持在细胞内。后两者是由铁储存分子实现的，这些分子存在于从最简单到最复杂的所有细胞类型中。铁储存蛋白属于铁蛋白超家族，具有不同寻常的结构，由24个亚基组成，形成一个围绕中心空腔的大球形蛋白质壳，可存储多达4500个铁原子。细菌是最简单的生物体，通常含有两种不同类型的铁蛋白：一种是铁蛋白（Ftn），它与哺乳动物中发现的原型铁蛋白非常相似；另一种是细菌铁蛋白（BFR），它与含血红素的蛋白质关系较远，迄今为止只在细菌中发现。我们和其他人已经研究了模型细菌大肠杆菌中的这些铁储存蛋白，从而详细了解了它们的合成是如何被控制的，以及它们是如何能够储存大量铁的。在环境缺铁的时候，细菌和其他生物调动它们的铁储备来弥补外部铁的缺乏。然而，无论是在细菌中还是在哺乳动物等更复杂的生物中，人们对铁是如何从铁储存中释放出来的知之甚少。我们和其他人已经确定了一个小的电子转移蛋白Bfd，我们认为它在BFR的铁动员中起关键作用。我们现在希望测试我们的假设，并首次在任何生物体中描述从铁储存蛋白中动员铁的过程。这里提出的研究独特地汇集了我们在铁代谢生理学（雷丁大学）和铁储存蛋白生物化学（东英吉利大学）方面的专业知识，以解决铁代谢这一主要遗留问题。采用真正的多学科方法，采用广泛的遗传、生化和生物分析方法，我们将详细研究大肠杆菌中BFR和Ftn的铁动员，以及Bfd和其他相关因素在这一过程中所起的作用。我们还将阐明BFR和Ftn在铁储存过程中的各自作用（目前尚不清楚为什么大肠杆菌和其他细菌具有两种不同的铁储存蛋白），并寻求确定与这些蛋白相互作用的其他细胞因子。这项工作将对我们理解细菌如何利用以前储存的铁进行合成过程产生重大影响。与BB/D001943/1接头。

项目成果

Crystal structure and metal binding properties of the periplasmic iron component EfeM from Pseudomonas syringae EfeUOB/M iron-transport system.

• DOI: 10.1007/s10534-022-00389-2
• 发表时间: 2022-06
• 期刊: BIOMETALS
• 影响因子: 3.5
• 作者: Rajasekaran, Mohan B.;Hussain, Rohanah;Siligardi, Giuliano;Andrews, Simon C.;Watson, Kimberly A.
• 通讯作者: Watson, Kimberly A.