Folding and stability of the beta adrenergic receptor

β肾上腺素能受体的折叠和稳定性

• 批准号: BB/G002037/1
• 负责人: Paula Booth
• 金额: $ 56.13万
• 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%2FG002037%2F1
• 关键词: Folding; stability; beta; adrenergic; receptor

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. This project aims to design a new method to study a particular type of protein, membrane proteins. In particular, it is focussed on a protein that acts as a receptor during communication between cells. This receptor is a member of the largest family of membrane proteins in the human genome, a family that is the major target for the development of new medicines. Unfortunately, there is a limited understanding of how these membrane receptor 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 work out what makes the receptor unstable and investigate how to ensure it folds correctly.

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。该项目旨在设计一种新的方法来研究一种特殊类型的蛋白质--膜蛋白。特别是，它集中在一种蛋白质上，这种蛋白质在细胞之间的交流中充当受体。该受体是人类基因组中最大的膜蛋白家族的成员，该家族是新药开发的主要靶点。不幸的是，对这些膜受体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。我们打算找出是什么使受体不稳定，并研究如何确保它正确折叠。

项目成果

Complete Reversible Refolding of a G-Protein Coupled Receptor on a Solid Support.

• DOI: 10.1371/journal.pone.0151582
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Di Bartolo N;Compton EL;Warne T;Edwards PC;Tate CG;Schertler GF;Booth PJ
• 通讯作者: Booth PJ

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