Lipid control of membrane protein folding

蛋白质是生命中的“工人分子”。我们身体中的细胞通过嵌入细胞膜中的蛋白质与外界进行感知和交流。这些膜蛋白约占我们体内蛋白质的三分之一，也是目前新药的一半以上。不幸的是，人们对膜蛋白在分子水平上如何工作的理解有限。这是因为它们在膜外非常不稳定，很难获得足够的数量用于科学研究。然而，最近的进展正在开始改变这种状况。我们的目标是设计新的方法来研究一种被称为“折叠”的现象。基因携带着蛋白质的密码，但在破译遗传信息如何被翻译成功能蛋白质方面仍然存在难题。蛋白质开始是一串氨基酸，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，灾难就会发生，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膜蛋白。我们建议通过设计新的方法来理解膜蛋白折叠来开拓新的领域。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。这些脂质分子是细胞膜的基本组成部分，有效地构成了这些生物壁，它们影响着邻近蛋白质的行为。我们已经知道某些脂质性质可以用来改变蛋白质折叠，我们现在的目标是了解这种控制的精确细节。

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.