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：
7233667
负责人：
David Salom
金额：
$ 36.59万
依托单位：
POLGENIX, 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 2008-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7233667
关键词：
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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. Our goal is to generate large amounts of purified homogenous receptor sample for each one of the 12 human 5-HT receptor subtypes. 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）：5-羟色胺（5-HT）是一种神经递质，与许多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，痴迷和恐慌症，恐慌和恐慌症，偏头痛和饮食失调。有12个5-HT受体亚型具有相似的识别特性，但属于G蛋白偶联受体（GPCR）家族的生理作用广泛，从而阻碍了亚型选择性药物的发现。对这些受体的三维结构的了解将使选择性药物的设计。但是，解决膜蛋白（例如GPCR）的原子分辨率下的结构受到了净化足够量均质和功能性蛋白质的困难。在这里，提出了一种新颖的专有表达系统，并结合了一种纯化方法，可以生成大量的高质量纯化受体，这可以解决瓶颈的结构阐明这些重要的药物靶标。我们的目标是为12个人类5-HT受体亚型中的每一种生成大量纯化的同质受体样品。这种高质量纯化的材料将是一种高度有价值的产品，可实现这些受体的结构阐明。