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Tail-anchored protein biogenesis: defining the ATP dependent route

尾锚定蛋白生物发生：定义 ATP 依赖性途径

基本信息

批准号：
BB/D007879/1
负责人：
Stephen High
金额：
$ 31.03万
依托单位：
University of Manchester
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%2FD007879%2F1
关键词：
Tail anchored protein biogenesis defining

项目摘要

Living things are made up of cells, and cells need membranes to provide barriers inside the cell and to protect them from the outside world. Whilst the biological membranes that form these barriers are incredibly complex and diverse in nature, they are generally characterised by a lipid bilayer that is studded with many proteins. Cells must normally replenish and renew their membranes by making new ones, and a key part of this process is the insertion or stitching of new proteins into the lipid bilayer. In more complex cells, such as those that make up our body, this integration of membrane proteins is one of the key functions of a specialised compartment known as the endoplasmic reticulum. As is the case for many biological processes, it has become clear that there are different ways of integrating a protein into the lipid bilayer of the endoplasmic reticulum. One mechanism is now fairly well understood and can be described as the 'classical' route for membrane proteins synthesis at the endoplasmic reticulum. Whilst the precise details of this classical pathway remain to be fully determined, we know most of the cellular factors and machineries that mediate it. In contrast, a second quite different pathway has been far less well studied so we know very little about the cellular components that are responsible for it or exactly what they do. This second pathway is used to make an important class of molecules called tail-anchored membrane proteins that are characteristic of more complex cells such as our own. The aim of this project is to identify the cellular machines that are responsible for putting tail-anchored proteins into the membrane of the endoplasmic reticulum. We will make use of the fact that we can now replicate this second pathway in a test tube, allowing us to compare how well different combinations of cellular components can carry out tail-anchored protein insertion. We are particularly interested in looking at the contribution of cellular machines known as molecular chaperones, since we have good reason to believe they play a major role in putting tail-anchored proteins into the endoplasmic reticulum. There are many different chaperones, and our work will tell us which particular chaperones are important for the second pathway and what exactly it is that they do during this process.

生物是由细胞组成的，细胞需要膜在细胞内提供屏障，保护细胞不受外部世界的影响。虽然形成这些屏障的生物膜在性质上是令人难以置信的复杂和多样化的，但它们的特征通常是含有许多蛋白质的脂双层。正常情况下，细胞必须通过制造新的细胞膜来补充和更新细胞膜，而这个过程的一个关键部分是将新的蛋白质插入或缝合到脂质双层中。在更复杂的细胞中，例如那些构成我们身体的细胞，这种膜蛋白的整合是内质网这一特殊隔间的关键功能之一。正如许多生物过程的情况一样，将蛋白质整合到内质网的脂质双层中的方法已经变得很明显。其中一种机制现在已经被很好地理解，可以被描述为内质网合成膜蛋白的“经典”途径。虽然这一经典途径的确切细节仍未完全确定，但我们知道大多数调节它的细胞因素和机制。相比之下，另一种完全不同的途径则研究得很少，因此我们对负责它的细胞成分或它们的确切作用知之甚少。第二条途径被用来制造一类重要的分子，称为尾部锚定的膜蛋白，它是像我们自己这样更复杂的细胞的特征。这个项目的目的是识别负责将尾部锚定的蛋白质放入内质网膜的细胞机器。我们将利用这样一个事实，即我们现在可以在试管中复制第二条途径，使我们能够比较不同细胞成分组合进行尾部锚定蛋白质插入的效果。我们特别感兴趣的是被称为分子伴侣的细胞机器的贡献，因为我们有充分的理由相信，它们在将尾部锚定的蛋白质放入内质网的过程中发挥着重要作用。有许多不同的伴侣，我们的工作将告诉我们，哪些特定的伴侣对第二条途径是重要的，以及它们在这个过程中到底做了什么。