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Purification and functional characterisation of COMATOSE a peroxisomal ABC transporter from Arabidopsis thaliana

拟南芥过氧化物酶体 ABC 转运蛋白 COMATOSE 的纯化和功能表征

基本信息

批准号：
BB/F007299/1
负责人：
Alison Baker
金额：
$ 46.68万
依托单位：
University of Leeds
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%2FF007299%2F1
关键词：
Purification functional characterisation COMATOSE peroxisomal

项目摘要

Cells of higher organisms such as plants and animals are divided into compartments that contain specific biological functions. Each compartment is surrounded by a membrane which acts as a barrier to movement of most biological molecules. In order for the activities of different compartments to proceed, the controlled transport of molecules across membranes has to occur. In most cases transport is mediated by proteins (transporters) within the membrane and often expenditure of energy is required to move the transported molecules against a concentration gradient. ABC transporters are a large class of membrane proteins which transport a wide range of biological molecules using energy released by breakdown of ATP, the principal 'energy currency' of living organisms. This proposal is concerned with one specific ABC transporter found in the membrane of the cellular compartment known as the peroxisome. Peroxisomes carry out a range of different biological functions but the one of particular interest to this project is beta-oxidation. In this pathway fat-like molecules are chopped up by sequential removal of 2 carbon atoms at a time. Different molecules may be subjected to beta-oxidation for different purposes - to provide energy, to remove unwanted molecules or to generate molecules with different biological activities, such as hormones. Peroxisome membranes of plants, animals and yeast contain similar ABC transporter proteins. There is quite good evidence in the case of yeast and plants that these proteins are involved in transporting fats into peroxisomes to be broken down. This may also be the case in animals, but the evidence is not so clear. What is clear is that plants and animals which have defective peroxisomal ABC transporters are very sick. Children born with a defective peroxisome ABC transporter called ALDP may develop a severe neurological disorder called Childhood Cerebral X-linked Adrenoleukodystrophy which results in progressive disability and death, and for which there is no cure and limited ameliorative treatment. Plant seeds with a defect in the equivalent ABC transporter (called CTS) can't germinate unless special tricks are used, have some hormone deficiencies and are less fertile than wild-type plants. We don't know to what extent the plant, yeast and human peroxisomal ABC transporters do the same things, but since they probably share a common evolutionary origin there is a good chance some functions are conserved. We will seek to investigate this by finding out if the plant transporter can function in place of the yeast transporter and if the human and yeast transporters can function in place of the plant transporter. We will also find out more about the precise functions of the plant transporter by investigating which molecules it can transport and what parts of the protein are necessary for this activity. By learning about the activity of this plant protein we would hope to understand how we could manipulate it to produce improved crop varieties. Understanding the similarities and differences between the plant, yeast and human transporters might also yield new insights into what the human transporter is doing which could be of benefit to understanding the pathology of X-linked Adrenoleukodystrophy.

高等生物如植物和动物的细胞被分成含有特定生物功能的隔间。每个隔室周围都有一层膜，膜起到了阻挡大多数生物分子运动的作用。为了使不同隔室的活动继续进行，必须发生分子跨膜的受控运输。在大多数情况下，转运是由膜内的蛋白质(转运体)介导的，通常需要消耗能量来移动被运输的分子，使其与浓度梯度相反。ABC转运蛋白是一大类膜蛋白，它利用生物体主要的“能量货币”--三磷酸腺苷的分解所释放的能量来运输广泛的生物分子。这项建议涉及一种特殊的ABC转运蛋白，发现于细胞室的膜上，称为过氧酶体。过氧化酶体执行一系列不同的生物功能，但这个项目特别感兴趣的一个是β-氧化。在这个途径中，类脂肪分子通过一次连续移除两个碳原子而被切割。不同的分子可能会受到不同目的的β-氧化作用--提供能量、去除不需要的分子或产生具有不同生物活性的分子，如激素。植物、动物和酵母的过氧化酶体膜含有相似的ABC转运蛋白。在酵母和植物中，有相当好的证据表明，这些蛋白质参与了将脂肪运输到要被分解的过氧化物体的过程中。在动物身上可能也是如此，但证据并不那么明确。有一点是清楚的，含有有缺陷的过氧体ABC转运蛋白的动植物是非常病态的。患有名为ALDP的过氧化物体ABC转运体缺陷的儿童可能会发展成一种严重的神经疾病，称为儿童期大脑X-连锁肾上腺脑白质营养不良，导致进行性残疾和死亡，目前尚无治愈和有限的改善治疗。在ABC转运蛋白(称为CTS)中有缺陷的植物种子不能发芽，除非使用特殊的技巧，而且有一些激素缺乏，而且比野生型植物的可育性差。我们不知道植物、酵母和人类过氧体ABC转运蛋白在多大程度上具有相同的功能，但由于它们可能具有共同的进化起源，因此很有可能某些功能是保守的。我们将通过找出植物转运蛋白是否可以取代酵母转运蛋白以及人类和酵母转运蛋白是否可以取代植物转运蛋白来进行研究。我们还将通过研究植物转运蛋白可以运输哪些分子以及蛋白质的哪些部分是这一活动所必需的，来更多地了解植物转运蛋白的确切功能。通过了解这种植物蛋白质的活性，我们希望了解我们如何操纵它来培育出改良的作物品种。了解植物、酵母和人类转运蛋白之间的异同也可能对人类转运蛋白的作用产生新的见解，这可能有助于理解X连锁肾上腺脑白质营养不良的病理。