Nature's solution to the iron problem: Mechanisms of iron management in ferritins

铁问题的自然解决方案：铁蛋白中铁的管理机制

基本信息

批准号：
BB/I021884/1
负责人：
Nicolas Le Brun
金额：
$ 43.18万
依托单位：
University of East Anglia
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2012
资助国家：
英国
起止时间：
2012 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FI021884%2F1
关键词：
Nature solution iron problem Mechanisms

项目摘要

Iron is essential for virtually all forms of life, playing central roles in many of the reactions on which life depends. Although this metal is highly abundant in the earth's crust, it is largely 'locked up' in minerals that are highly insoluble and this severely limits its availability to living organisms. The scarcity of iron has led to the evolution in microbes of many ingenious mechanisms to obtain sufficient quantities to sustain growth. These include the secretion and re-absorption of small organic molecules that can bind iron very tightly and therefore hoover up what iron there is. Pathogenic bacteria can effectively steal iron from iron-containing proteins in their hosts, and the success of such mechanisms is a key determinant of whether or not a successful infection is established. Another important aspect of how cells overcome the iron problem, is their ability to store iron. This is achieved through a remarkable family of proteins known as ferritins. These can be thought of as being football-like molecules with a hollow centre, inside which thousands of iron atoms can be stored in the form of an iron mineral - one that would form insoluble precipititates were it not for the solubilising effect of the protein coat. The storage of iron serves two important functions. Firstly, it enables microbes to draw on reserves when iron in the immediate environment becomes particularly low, and secondly, it overcomes the potential toxicity of iron that results from the very properties that make it useful to life: without proper control, iron can lead to the generation of reactive oxygen species that can cause severe cellular damage. In this research we propose to better understand how two particular ferritins from two very different microbes take up iron and orchestrate the deposition of their iron mineral cargo, and how they subsequently release it. One of these is from the organism Escherichia coli - a bacterium that has for decades been a workhorse for understanding cellular processes, but which can also be pathogenic. The other ferritin is one that was very recently identified in phytoplankton. These organisms are responsible for a large proportion of the primary production of organic molecules from carbon dioxide in the oceans. Furthermore, they also form spectacular blooms in areas of temporary nutrient sufficiency. In many areas, the growth limiting nutrient is iron and it is now known that the presence of ferritin in these phytoplankton is crucial for their ability to utilise temporarily available iron. This research will lead to a significant advance in our understanding of iron cycling processes and of the relationship between structural and functional properties of ferritins. This will also have more general impact in understanding the reactivities of iron proteins and in protein-driven biomineralisation processes.

铁对于几乎所有形式的生活都是必不可少的，在生活依赖的许多反应中扮演着核心角色。尽管这种金属在地壳中高度丰富，但它在很大程度上是“锁定的”矿物质，这些矿物质高度不溶，这严重限制了其对生物体的可用性。铁的稀缺导致了许多巧妙机制的微生物的发展，以获得足够数量的维持增长。这些包括分泌和重新吸收小的有机分子，这些有机分子可以非常紧密地结合铁，从而使铁的结合。致病细菌可以有效地从其宿主中的含铁蛋白中窃取铁，这种机制的成功是确定是否成功感染的关键决定因素。细胞如何克服铁问题的另一个重要方面是它们储存铁的能力。这是通过一个非凡的蛋白质家族来实现的，称为铁蛋白。这些可以被认为是带有空心中心的足球状分子，可以在其中以铁矿物质的形式存储成千上万的铁原子 - 如果不是为了蛋白质涂层的溶解作用，它将形成不溶性沉淀。铁的存储具有两个重要功能。首先，当铁在直接环境中变得特别低时，它使微生物能够利用储量，其次，它克服了铁的潜在毒性，这是由于使其对生命有用的特性所产生的潜在毒性：如果没有适当的控制，铁就可以导致产生的反应性氧，从而导致严重的细胞损伤。在这项研究中，我们建议更好地了解来自两个截然不同的微生物的两种特定的铁蛋白如何占据铁并策划其铁矿货物的沉积，以及它们随后如何释放。其中之一来自生物体大肠杆菌 - 一种细菌，几十年来一直是理解细胞过程的主力，但也可能是致病性的。另一种铁蛋白是最近在浮游植物中发现的铁蛋白。这些生物是从海洋中二氧化碳产生的主要产生有机分子的大部分。此外，它们在临时营养充足的地区还形成了壮观的花朵。在许多地区，限制养分的生长是铁，现在众所周知，这些浮游生素在这些浮游生物中的存在对于使用暂时可用的铁的能力至关重要。这项研究将导致我们对铁循环过程以及铁蛋白的结构和功能特性之间关系的显着进步。这也将对理解铁蛋白的反应性和蛋白质驱动的生物矿化过程产生更大的影响。