Lipid control of membrane protein folding

膜蛋白折叠的脂质控制

• 批准号: BB/F013183/1
• 负责人: Paula Booth
• 金额: $ 79.45万
• 依托单位: University of Bristol
• 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%2FF013183%2F1
• 关键词: Lipid; control; membrane; protein; folding

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“工作分子”。我们体内的细胞通过嵌入在细胞周围的膜中的蛋白质来感知并与外部世界交流。这些膜蛋白约占我们体内蛋白质的三分之一，是目前新药靶标的一半以上。不幸的是，对于膜蛋白如何在分子水平上发挥作用，人们的理解是有限的。这是因为它们在膜外是出了名的不稳定，很难获得足够的量来进行科学研究。然而，最近的进展正开始改变这一局面。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转化为功能蛋白质方面仍然存在谜团。蛋白质最初是一串氨基酸，然后必须在身体的右侧折叠成特定的形状。如果折叠失败，灾难就会降临，蛋白质就会失灵。在对这种折叠现象的认识中，最明显的空白来自于膜蛋白。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。我们打算通过专注于膜的另一个主要成分：脂类来实现这一点。这些脂质分子是膜的基本构件，有效地构成了这些生物墙的砖块，它们影响着邻近蛋白质的行为。我们已经知道某些脂质属性可以用来改变蛋白质折叠，现在我们的目标是了解这种控制的确切细节。

项目成果

Retinal proteins as model systems for membrane protein folding.

视网膜蛋白作为膜蛋白折叠的模型系统。

• DOI: 10.1016/j.bbabio.2013.11.021
• 发表时间: 2014
• 期刊: Biochimica et biophysica acta
• 作者: Tastan O

Encyclopedia of Biophysics

生物物理学百科全书

• DOI: 10.1007/978-3-642-16712-6_41
• 发表时间: 2013
• 作者: Munro A