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：
Abattoirs Accounting Achievement Amino Acids Antibodies Anxiety Area Atomic Force Microscopy Authorization documentation Automobile Driving Award Biochemical Bioreactors Bos taurus Budgets Businesses C-terminal Cattle Cells Collaborations Count Crystallization Cyclic GMP DNA Destinations Detergents Development Disease Disruption Drug Delivery Systems Drug Design Dynamin Eating Disorders Endoplasmic Reticulum Enhancers Ensure Etiology Eye Family Figs - dietary Fluorescence Future G-Protein-Coupled Receptors GTP-Binding Proteins Generations Genes Goals Grant Green Fluorescent Proteins HTR2A gene Hand Heterogeneity Human Human Genome Hypertension Image Imagery In Vitro Investigation Irritable Bowel Syndrome Knock-in Mouse Knockout Mice Knowledge Laboratories Left Letters Ligand Binding Light Marketing Mechanics Mediating Membrane Membrane Proteins Mental Depression Mental disorders Methods Migraine Modeling Molecular Conformation Mus National Institute of Mental Health Neurons Neurotransmitters Obesity Ophthalmology Panic Disorder Pathway interactions Pattern Pharmaceutical Preparations Pharmacologic Substance Phase Photons Photophobia Photoreceptors Physiological Physiological Processes Population Preparation Principal Investigator Process Production Property Protein Export Pathway Proteins Rate Reading Regulation Research Research Personnel Resolution Rest Retina Retinal Degeneration Rhodopsin Risk Rod Outer Segments Role Sales Sampling Schizophrenia Scientist Second Messenger Systems Secure Sensory Serotonin Side Signal Transduction Site Small Business Funding Mechanisms Small Business Innovation Research Grant Social Phobia Source Spottings Staging Structural Models Structure System Tadpoles Technology Testing Therapeutic Therapeutic Agents Time TimeLine Transgenic Mice Transgenic Organisms Translations Universities Visual system structure Vomiting Washington Work X-Ray Crystallography Xenopus Xenopus laevis Xenopus oocyte absorption base commercialization density design desire dimer disease-causing mutation drug discovery extracellular genetic manipulation glycosylation human CCXCR1 receptor improved in vivo interest milligram molecular modeling novel polypeptide prevent professor programs promoter protein function protein misfolding protein structure receptor receptor expression retinal rods rho rod outer segment disc scale up second messenger serotonin receptor success three dimensional structure tool

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）：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。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均质受体样本。这种高质量的纯化材料将是一种非常有价值的产品，能够阐明这些受体的结构。