Purified Serotonin Receptors for Structural Studies

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。G蛋白偶联受体（gpcr）家族共有12种5-HT受体亚型，它们具有相似的识别特性，但生理作用差异很大，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设计选择性药物成为可能。然而，在原子分辨率上解决膜蛋白（如gpcr）的结构一直受到纯化足够数量的均质和功能蛋白的困难的阻碍。本文提出了一种新颖的专有表达系统，结合纯化方法，产生大量高质量的纯化受体，可以解决这些重要药物靶点结构解析的瓶颈。我们的目标是为12种人类5-HT受体亚型中的每一种产生大量纯化的同质受体样本。这种高质量的纯化材料将是一种非常有价值的产品，可以阐明这些受体的结构。

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.