Ultra-High Resolution Structure and Dynamics of Bilayer Bound Polypeptides

双层结合多肽的超高分辨率结构和动力学

• 批准号: 9317111
• 负责人: Timothy Cross
• 金额: $ 34.5万
• 依托单位: Florida State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-01-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9317111&HistoricalAwards=false
• 关键词: Ultra; Resolution; Structure; Dynamics; Bilayer

9317111 Cross Dr. Cross will continue the development of solid state NMR spectroscopy for the determination of macromolecular structure and dynamics in samples experiencing an anisotropic environment. The efforts here focus on peptides bound in lipid bilayers where the global motions are restricted to the axial rotation about the bilayer normal. Local motions will be characterized in detail and a thorough investigation of correlated motions that may extend beyond the peptide into its environment will be sought. Very high resolution structural information will be obtained from orientational constraints which have already been shown to have a very level of accuracy. Through such a dynamic and structural characterization it is hoped that a more detailed view of the potential energy surfaces of the polypeptide backbone can be achieved. Furthermore, correlations between dynamic rates and kinetic rates may lead to unprecedented descriptions of relationships between structure dynamics and function. To achieve these goals a variety of solid state NMR techniques will be refined and combined with unique sample preparation schemes that both orient lipid bilayers and their host peptides as well as specific site isotopically labeled molecules. %%% The development of methods for the determination of macromolecular structure for those proteins and other molecules that are not easily studied by the more traditional methods, such as x ray diffraction will be continued. The approach taken here will utilize Nuclear Resonance spectroscopy of samples that have one dimensional order, such as an oriented film. In this way all molecules are aligned with respect to the magnetic field of the instrument and structural constraints are readily achieved. Membrane bound proteins are a very important class of biological macromolecules that are responsible for much of the communication between cells in living tissue. For x ray diffraction it has been very difficult to form cocrystals of these proteins and the lipid molecules that make up their membrane environment. However, it has been possible to form uniformly aligned samples for the NMR spectroscopy and therefore, this method is expected to play a very important role in the structure determination of this important class of proteins. ***

9317111 Cross Cross博士将继续开发固态NMR光谱，用于确定经历各向异性环境的样品中的大分子结构和动力学。 这里的努力集中在肽结合在脂质双层的全球运动被限制到轴向旋转的双层正常。 局部运动的特点是详细和相关的运动，可能会超出肽到其环境中的彻底调查将寻求。 非常高分辨率的结构信息将获得定向约束，已经被证明有一个非常高的精度。 通过这样的动态和结构表征，希望可以实现多肽骨架的势能表面的更详细的视图。 此外，动态速率和动力学速率之间的相关性可能会导致前所未有的结构动力学和功能之间的关系的描述。 为了实现这些目标，将改进各种固态NMR技术，并将其与独特的样品制备方案相结合，该方案既定位脂质双层及其宿主肽，也定位特定位点的同位素标记分子。将继续发展用较传统的方法如X射线衍射法不易研究的蛋白质和其他分子的大分子结构测定方法。 这里采用的方法将利用具有一维顺序的样品的核共振光谱，例如取向膜。 以这种方式，所有分子相对于仪器的磁场对齐，并且容易实现结构约束。 膜结合蛋白是一类非常重要的生物大分子，负责活组织中细胞之间的大部分通信。 对于x射线衍射来说，很难形成这些蛋白质和构成其膜环境的脂质分子的共晶。 然而，它已经有可能形成均匀排列的样品的NMR光谱，因此，这种方法预计将在这类重要的蛋白质的结构测定中发挥非常重要的作用。***