STRUCTURAL AND DYNAMICAL STUDIES OF OMP USING NMR

使用 NMR 对 OMP 进行结构和动力学研究

• 批准号: 6489593
• 负责人: DONNA M BALDISSERI
• 金额: $ 7.43万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6489593
• 关键词: nerve /myelin protein; nuclear magnetic resonance spectroscopy; protein structure function; relaxation spectrometry

OMP, the olfactory maker protein, is an abundant protein whose expression is restricted almost exclusively, to mature olfactory neurons. Since its discovery nearly 30 years ago, by the co-I, OMP has been used by many laboratories as the definitive identifier of mature olfactory neurons. The primary sequence of OMP is phylogenetically conserved across vertebrate species and is 55% identical from Xenopus to human. In addition, the organization and sequence of the OMP gene promoter is conserved in several mammals. Nevertheless, OMP has no homologs in the databases and, until recently, its function in olfactory sensory neurons has been elusive. The recent generation of OMP-null mice has provided clear in vivo and in vitro evidence for the involvement of OMP as a novel participant in the olfactory signal detection/transduction cascade. To study this at the protein structural level we propose to use NMR spectroscopy of isoptically labeled OMP to solve its structure and its dynamical properties. Knowledge of OMP's structure and dynamics will provide a structural context for characterization of its intrinsic functionality and that which is associated with its interaction(s) with other components of the olfactory signal detection/transduction cascade. Further, this study represents the first NMR structural solution for any protein involved in chemosensory transduction.

嗅觉标记蛋白OMP是一种丰富的蛋白质，其表达几乎仅限于成熟的嗅觉神经元。自从近30年前由co-I发现以来，OMP已被许多实验室用作成熟嗅觉神经元的确定性鉴定物。OMP的一级序列在脊椎动物物种中是遗传上保守的，并且从非洲爪蟾到人类具有55%的相同性。此外，OMP基因启动子的结构和序列在几种哺乳动物中是保守的。然而，OMP在数据库中没有同源物，直到最近，它在嗅觉感觉神经元中的功能一直是难以捉摸的。最近一代的OMP-空小鼠提供了明确的在体内和体外证据参与OMP作为一种新的参与者在嗅觉信号检测/转导级联。为了在蛋白质结构水平上研究这一点，我们建议使用NMR光谱的isopticallabeled OMP解决其结构和动力学性质。OMP的结构和动力学的知识将提供表征其内在功能的结构背景，以及与其与嗅觉信号检测/转导级联的其他组分的相互作用相关的结构背景。此外，这项研究代表了第一个NMR结构的解决方案，任何蛋白质参与化学传感转导。