CAREER: Solid-State Nuclear Magnetic Resonance Studies of Elastin and its Related Polypeptides

PI将进行现代高分辨率固态核磁共振（NMR）实验，以表征不溶性弹性蛋白的分子结构。首先，二级结构元素和交联分子将分别通过13C和15N化学位移测量来确定。固体核磁共振实验将用于确定不同样品条件的影响，以探测分子内相互作用的作用。此外，还将研究正常小鼠和转基因小鼠的弹性蛋白。核磁共振谱的差异将指示分子结构与正常生理功能之间的关系。最后，将研究与弹性蛋白相关的模型肽系统。不溶性弹性蛋白负责哺乳动物生理结构的弹性，如血管、韧带和皮肤。然而，由于缺乏目前可用的高分辨率结构数据，对弹性分子基础的基本理解是薄弱的。这项工作将集中于阐明正常和缺陷弹性蛋白的结构信息，以及被认为是该蛋白模型系统的肽。在这些系统上收集的数据将用于深入了解弹性蛋白的结构-性质关系。这项研究是高度跨学科的，涉及从固态核磁共振到分子生物学等多种主题；本着这一理念，将为研究生和本科生提供现代化的学习环境，无论是在课堂上还是在实验室里。

9733035 Kumashiro The PI will conduct modern high-resolution solid-state nuclear magnetic resonance (NMR) experiments to characterize the molecular structure of insoluble elastin. Initially, secondary structural elements and the crosslinking moeities will be identified by 13C and 15N chemical shift measurements, respectively. Solid-state NMR experiments will then be used to ascertain the effect of different sample conditions, to probe the intramolecular interactions at work. In addition, elastin from normal and transgenic mice will be studied. The differences in NMR spectra will be indicative of the relationships between molecular structure and normal physiological function. Finally, model peptide systems related to elastin will be studied. Insoluble elastin is responsible for the elasticity in physiological structures in mammals, like blood vessels, ligaments, and skin. However, a fundamental understanding of the molecular basis of elasticity is weak, due to the lack of high-resolution structural data that is presently available. This work will focus on the elucidation of structural information on normal and defective elastin, as well as the peptides thought to be model systems for this protein. The data gathered on these systems will then be used to gain insight into the structure-property relationships of elastin. This research is highly interdisciplinary, drawing on topics as diverse as solid-state NMR to molecular biology; with this philosophy in mind, a modern learning environment for graduate and undergraduate students, both in the classroom and in the laboratory, will be provided.