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/G003653/1
• 负责人: Chris Tate
• 金额: $ 45.81万
• 依托单位: MRC Centre Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FG003653%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。该项目旨在设计一种新方法来研究特定类型的蛋白质——膜蛋白。特别是，它专注于在细胞间通讯过程中充当受体的蛋白质。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目标。不幸的是，人们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。我们打算找出导致受体不稳定的原因，并研究如何确保其正确折叠。

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

A mutagenesis and screening strategy to generate optimally thermostabilized membrane proteins for structural studies.

一种诱变和筛选策略，以生成最佳的恒温膜蛋白进行结构研究。

• DOI: 10.1038/nprot.2016.088
• 发表时间: 2016-08
• 期刊: Nature protocols
• 影响因子: 14.8
• 作者: Magnani F;Serrano-Vega MJ;Shibata Y;Abdul-Hussein S;Lebon G;Miller-Gallacher J;Singhal A;Strege A;Thomas JA;Tate CG
• 通讯作者: Tate CG

Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation.

• DOI: 10.1038/nature10136
• 发表时间: 2011-05-18
• 期刊: NATURE
• 影响因子: 64.8
• 作者: Lebon, Guillaume;Warne, Tony;Edwards, Patricia C.;Bennett, Kirstie;Langmead, Christopher J.;Leslie, Andrew G. W.;Tate, Christopher G.
• 通讯作者: Tate, Christopher G.