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Lipid control of membrane protein folding

膜蛋白折叠的脂质控制

基本信息

批准号：
BB/F013167/1
负责人：
Richard Templer
金额：
$ 88.59万
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF013167%2F1
关键词：
Lipid control membrane protein folding

项目摘要

Proteins are the 'worker molecules' in life. Cells in our bodies sense and communicate with the outside world via proteins embedded in membranes that surround the cells. These membrane proteins constitute about a third of the proteins in our bodies, and over half of the current targets for new medicines. Unfortunately, there is a limited understanding of how membrane proteins work at a molecular level. This is because they are notoriously unstable outside the membrane and it is difficult to obtain sufficient amounts for scientific study. Recent advances are, however, beginning to alter this situation. We aim to devise new methods to study a phenomenon known as 'folding'. Genes carry the code for proteins, but puzzles remain in deciphering how genetic information is translated into functional proteins. Proteins begin as a string of amino acids, which then have to fold-up to a particular shape in the right part of the body. If this folding fails, disaster strikes and the proteins malfunction. The most glaring gaps in knowledge of this folding phenomenon come with membrane proteins. We propose to forge new territory by devising new methods to understand membrane protein folding. We intend to do this by focussing on the other main component of membranes: lipids. These lipid molecules are the basic building blocks of membranes, effectively the bricks that make up these biological walls and they influence how their neighbouring proteins behave. We already know that certain lipid properties can be used to alter the protein folding and we now aim to understand the precise details of this control.

蛋白质是生命中的“工人分子”。我们体内的细胞通过嵌入细胞周围膜中的蛋白质来感知外界并与外界沟通。这些膜蛋白约占我们体内蛋白质的三分之一，也是当前新药靶标的一半以上。不幸的是，人们对膜蛋白如何在分子水平上发挥作用的了解有限。这是因为它们在膜外非常不稳定，很难获得足够的量用于科学研究。然而，最近的进展开始改变这种情况。我们的目标是设计新方法来研究“折叠”现象。基因携带蛋白质的密码，但破译遗传信息如何转化为功能性蛋白质仍然是个谜。蛋白质最初是一串氨基酸，然后必须在身体的正确部位折叠成特定的形状。如果这种折叠失败，灾难就会降临，蛋白质就会发生故障。关于这种折叠现象的知识中最明显的空白来自于膜蛋白。我们建议通过设计新方法来理解膜蛋白折叠来开辟新领域。我们打算通过关注膜的另一个主要成分：脂质来做到这一点。这些脂质分子是膜的基本组成部分，实际上是构成这些生物墙的砖块，它们影响邻近蛋白质的行为。我们已经知道某些脂质特性可用于改变蛋白质折叠，现在我们的目标是了解这种控制的精确细节。