AR COBRE: MEMBRANE PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 生物物理研究是为了阐明生物膜中蛋白质和脂类之间的功能相互作用的关键方面。膜蛋白不仅是生物化学领域的重要前沿，也是整个科学领域的重要前沿。膜蛋白功能对细胞生理和生物功能的调节具有重要意义。该项目的一个关键目标将是开发和推进固态核磁共振光谱和荧光显微镜的实验方法，这些方法是解决蛋白质和脂类在生物膜内相互作用的机制所需的。由于生物膜的复杂性，这里提出的项目最初将利用精心设计的由小的疏水蛋白结构域组成的模型系统，这将为更复杂的系统的研究铺平道路。然后，我们将扩展这些方法来研究和表征一个更复杂的原型系统，即膜锚定的细胞色素P450酶。模型系统提供了两种方法来设置舞台：它们允许理解和洞察基本的分子相互作用；它们有助于开发实验技术，然后这些技术可以应用于其他(更大的)系统，如P450与膜结合的反应伙伴的络合物等。医疗保健的切实好处可能通过两种方式产生：模型和原型系统本身可能为诊断或临床医学中基于膜的干预提供新的战略。此外，所学的一般膜原理可以应用于膜生物学中的医学问题。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Biophysical investigations are proposed to elucidate key aspects of the functional interactions between proteins and lipids in biological membranes. Membrane proteins are an important frontier within not only biochemistry, but science generally. Membrane protein function has crucial implications for cell physiology and the regulation of biological function. A key goal of this project will be to develop and advance experimental methods in solid-state NMR spectroscopy and fluorescence microscopy that are needed for addressing the mechanisms by which proteins and lipids interact within biological membranes. Due to the complexity of biological membranes, the projects proposed here will, initially, make use of judiciously designed model systems that consist of small, hydrophobic protein domains and that will pave the way for studies of more complex systems. We then will extend the methods to investigate and characterize a prototype system of greater complexity, the membrane-anchored cytochrome P450 enzyme. The model systems provide two means for setting the stage: they allow understanding and insight into fundamental molecular interactions; and they lend themselves toward the development of experimental techniques that then become available for application to other (larger) systems, such as the complexes of P450 with membrane-bound reaction partners, and beyond. Tangible benefits for health care may accrue in two ways: The model and prototype systems themselves may suggest new strategies for membrane-based interventions in diagnostic or clinical medicine. Furthermore, the general membrane principles that are learned may be applied to medical issues in membrane biology.