Purified Serotonin Receptors for Structural Studies

用于结构研究的纯化血清素受体

基本信息

批准号：
6690933
负责人：
David Salom
金额：
$ 14.89万
依托单位：
NOVASITE PHARMACEUTICALS, INC.
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-01 至 2004-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6690933
关键词：
Xenopus Xenopus oocyte cell surface receptors method development protein purification protein structure rod cell serotonin receptor three dimensional imaging /topography

项目摘要

DESCRIPTION (provided by applicant): Serotonin (5-HT) is a neurotransmitter that has been implicated in the aetiology of numerous Mental Health disorders, including depression, anxiety, social phobia, schizophrenia, obsessive-compulsive and panic disorders, migraine, and eating disorders. There are 12 5-HT receptor subtypes with similar recognition properties yet widely divergent physiological roles that belong to the same family of G Protein Coupled Receptors (GPCRs), hindering the discovery of subtype-selective drugs. Knowledge of the 3-dimensional structure of these receptors would enable the design of selective drugs. However, solving the structure at atomic resolution of membrane proteins such as GPCRs has been hampered by the difficulty to purify sufficient amounts of homogeneous and functional protein. Here, it is proposed a novel, proprietary expression system combined with a purification method to generate large amounts of high quality purified receptor, which could solve the bottleneck for structural elucidation of these important drug targets. In Phase I, the feasibility of the proposed approach will be tested for all the 12 human 5-HT GPCRs. In Phase II, this approach will be developed resulting in purified homogenous protein for each human 5- HT receptor subtype. This high quality purified material will be a highly valuable product enabling structural elucidation of these receptors.

描述（由申请人提供）：血清素 (5-HT) 是一种神经递质，与多种精神健康疾病的病因有关，包括抑郁症、焦虑症、社交恐惧症、精神分裂症、强迫症和恐慌症、偏头痛和饮食失调。属于同一G蛋白偶联受体(GPCR)家族的12种5-HT受体亚型具有相似的识别特性，但生理作用却截然不同，这阻碍了亚型选择性药物的发现。了解这些受体的三维结构将使选择性药物的设计成为可能。然而，由于难以纯化足够量的同质和功能性蛋白质，以原子分辨率解析 GPCR 等膜蛋白的结构受到了阻碍。在这里，我们提出了一种新颖的、专有的表达系统与纯化方法相结合，以产生大量高质量的纯化受体，这可以解决这些重要药物靶点结构解析的瓶颈。在第一阶段，将针对所有 12 种人类 5-HT GPCR 测试所提出方法的可行性。在第二阶段，将开发这种方法，为每种人类 5-HT 受体亚型产生纯化的均质蛋白质。这种高质量的纯化材料将是一种非常有价值的产品，能够阐明这些受体的结构。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Heterologous expression of the adenosine A1 receptor in transgenic mouse retina.

转基因小鼠视网膜中腺苷 A1 受体的异源表达。

DOI：
发表时间：
2007-07-17
期刊：
影响因子：
2.9
作者：
Li, Ning;Salom, David;Zhang, Li;Harris, Tim;Ballesteros, Juan A;Golczak, Marcin;Jastrzebska, Beata;Palczewski, Krzysztof;Kurahara, Carole;Juan, Todd;Jordan, Steven;Salon, John A
通讯作者：
Salon, John A

Heterologous expression and purification of the serotonin type 4 receptor from transgenic mouse retina.

转基因小鼠视网膜中 4 型血清素受体的异源表达和纯化。

DOI：
发表时间：
2008-12-16
期刊：
影响因子：
2.9
作者：
Salom, David;Wu, Nan;Sun, Wenyu;Dong, Zhiqian;Palczewski, Krzysztof;Jordan, Steven;Salon, John A
通讯作者：
Salon, John A

Expression of functional G protein-coupled receptors in photoreceptors of transgenic Xenopus laevis.

转基因非洲爪蟾光感受器中功能性 G 蛋白偶联受体的表达。