权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of an improved SMALP toolkit to extract active membrane proteins

开发改进的 SMALP 工具包来提取活性膜蛋白

基本信息

批准号：
BB/S008160/1
负责人：
Timothy Dafforn
金额：
$ 71.74万
依托单位：
University of Birmingham
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FS008160%2F1
关键词：
Development improved SMALP toolkit extract

项目摘要

Life depends on tiny machines within our bodies made from protein. These machines have a wide range of functions from digesting our food, through to defending us from infection and allowing us to see. One of most important classes of protein machines is those that live in the membrane that surround cells. These membrane proteins allow nutrients into the cell and allow waste products to leave; they also mediate the movement of signals into and out of the cell. These functions make them exceptionally interesting to researchers, but perhaps more importantly they are also the most important targets for developing new therapeutics for plant and animal health. For example more than 50% of all drugs used today target these membrane proteins. Unfortunately these proteins have proved to be exceptionally difficult to study and have confounded a large number of scientists over the past 50 years. In 2009 we found an entirely new way of making these proteins by using a simple polymer more commonly found in car dashboards and paint. This method "wraps" the protein in a protective polymer "belt" that keeps it stable allowing us to study it. This new method has opened up a whole range of new opportunities for scientists to study these important proteins. This has included significant interest from scientists in pharmaceutical companies who have found that the method makes it a lot easier for them to develop new drugs. However as with any method, our method has some small but significant limitations that mean that it cannot currently be used to study all aspects of how these protein machines work. For example our method prevents these proteins from changing shape. Such changes are often important for the function of the protein. You could say that the polymer belt is not elastic enough! In this project we aim to develop a new improved "tool kit" that contains new polymers and new methods that we hope will allow these proteins to be studied. We are hoping to first work with academic scientists to ensure that the methods work with the most important families of proteins encountered in life. We will then extend our collaborations to encompass commercial scientists ensuring that progress in developing new drugs and agrochemicals continues at a rapid rate.

生命依赖于我们体内由蛋白质组成的微小机器。这些机器具有广泛的功能，从消化我们的食物，到保护我们免受感染，让我们看到。其中最重要的一类蛋白质机器是那些生活在细胞膜周围的蛋白质机器。这些膜蛋白允许营养物质进入细胞并允许废物离开;它们还介导信号进出细胞的运动。这些功能使它们对研究人员非常感兴趣，但也许更重要的是，它们也是开发植物和动物健康新疗法的最重要目标。例如，今天使用的所有药物中有超过50%针对这些膜蛋白。不幸的是，这些蛋白质已经被证明是非常难以研究的，并且在过去的50年里混淆了大量的科学家。2009年，我们发现了一种全新的方法来制造这些蛋白质，方法是使用一种简单的聚合物，这种聚合物更常见于汽车仪表板和油漆中。这种方法将蛋白质“包裹”在一个保护性的聚合物“带”中，使其保持稳定，使我们能够对其进行研究。这种新方法为科学家研究这些重要的蛋白质开辟了一系列新的机会。这包括制药公司的科学家的极大兴趣，他们发现这种方法使他们更容易开发新药。然而，与任何方法一样，我们的方法有一些小但重要的限制，这意味着它目前不能用于研究这些蛋白质机器如何工作的所有方面。例如，我们的方法可以防止这些蛋白质改变形状。这种变化通常对蛋白质的功能很重要。你可以说聚合物带不够弹性！在这个项目中，我们的目标是开发一个新的改进的“工具包”，其中包含新的聚合物和新的方法，我们希望将允许这些蛋白质进行研究。我们希望首先与学术科学家合作，以确保这些方法适用于生命中遇到的最重要的蛋白质家族。然后，我们将扩大我们的合作，包括商业科学家，确保在开发新的药物和农用化学品的进展继续以快速的速度。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Biophysical characterisation of SMALPs.

SMLP 的生物物理特征。

DOI：
10.1042/bst20201088
发表时间：
2021
期刊：
Biochemical Society transactions
影响因子：
3.9
作者：
Nestorow SA
通讯作者：
Nestorow SA

Conformational trapping of an ABC transporter in polymer lipid nanoparticles.

DOI：
10.1042/bcj20210312
发表时间：
2022-01-28
期刊：
The Biochemical journal
影响因子：
0
作者：
Pollock NL;Lloyd J;Montinaro C;Rai M;Dafforn TR
通讯作者：
Dafforn TR

The function of BK channels extracted and purified within SMALPs.

SMALP 内提取和纯化的 BK 通道的功能。

DOI：
10.1042/bcj20210628
发表时间：
2022-08-12
期刊：
The Biochemical journal
影响因子：
0
作者：
通讯作者：

Detergent-Free Membrane Protein Purification Using SMA Polymer.

DOI：
10.1007/978-1-0716-2368-8_21
发表时间：
2022-01-01
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
0
作者：
Broadbent, Luke;Depping, Peer;Rothnie, Alice J
通讯作者：
Rothnie, Alice J

Membrane protein extraction and purification using partially-esterified SMA polymers.

DOI：
10.1016/j.bbamem.2021.183758
发表时间：
2021-12-01
期刊：
Biochimica et biophysica acta. Biomembranes
影响因子：
0
作者：
Hawkins OP;Jahromi CPT;Gulamhussein AA;Nestorow S;Bahra T;Shelton C;Owusu-Mensah QK;Mohiddin N;O'Rourke H;Ajmal M;Byrnes K;Khan M;Nahar NN;Lim A;Harris C;Healy H;Hasan SW;Ahmed A;Evans L;Vaitsopoulou A;Akram A;Williams C;Binding J;Thandi RK;Joby A;Guest A;Tariq MZ;Rasool F;Cavanagh L;Kang S;Asparuhov B;Jestin A;Dafforn TR;Simms J;Bill RM;Goddard AD;Rothnie AJ
通讯作者：
Rothnie AJ