STRUCTURAL AND DYNAMICAL STUDIES OF OMP USING NMR

嗅觉制造蛋白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最终标识符。OMP的初级序列在整个脊椎动物物种中是保守的，从爪蟾到人类的相同度为55%。此外，OMP基因启动子的组织和序列在一些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缺失小鼠提供了明确的体内和体外证据，证明OMP作为一种新的参与者参与嗅觉信号检测/转导级联。为了在蛋白质结构水平上研究这一点，我们建议使用等光标记OMP的核磁共振波谱来解决其结构和动力学性质。了解OMP的结构和动力学将为表征其内在功能以及其与嗅觉信号检测/转导级联的其他组分的相互作用提供结构背景。此外，这项研究代表了任何参与化学感觉转导的蛋白质的第一个核磁共振结构解决方案。

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.