NMR Studies of Elastin Structure and Dynamics

该项目的目的是提供新的见解，生物弹性和其他性质的蛋白质，与疏水性。 皮肤和血管的独特弹性和弹性特性可以追溯到弹性蛋白，弹性蛋白是构成这些组织的大部分的纤维的主要蛋白质成分。弹性蛋白主要由散布有富含丙氨酸的交联区域的长疏水链组成。这种蛋白质的性质排除了使用经典的高分辨率结构工具，如晶体学和溶液NMR光谱。在NSF的CAREER计划的支持下，PI使用固态NMR结合同位素标记的新方法来阐明这种复杂生物聚合物的新结构信息。 在这个项目中，弹性蛋白和弹性蛋白肽的结构和动力学特性将得到扩展。 主要的焦点是使用固态NMR光谱从细胞培养物中同位素富集的不溶性弹性蛋白的结构表征。这些研究将通过合成和细菌表达的弹性蛋白肽的类似工作来补充。最后，这些系统的动态调查将继续进行。所有结果将被整合，以提供一个全面的生物弹性的图片。这项研究将涉及各个层次的学生-本科生，研究生和博士后。本文提供的研究培训经验是跨学科的，让学生接触到一系列的技术和专业知识，特别是因为该项目涉及弹性蛋白生物化学和基质生物学的几个合作者。

The objective of this project is to provide new insight into biological elasticity and other properties of proteins that are tied to hydrophobicity. The uniquely resilient and elastic properties of skin and blood vessels have been traced to elastin, the principal protein component of the fibers that comprise a large portion of these tissues. Elastin is comprised primarily of long hydrophobic chains interspersed with alanine-rich crosslinking regions. The very nature of this protein precludes the use of classic high-resolution structural tools, such as crystallography and solution NMR spectroscopy. With the prior support from the NSF's CAREER program, the PI used solid-state NMR in conjunction with a novel approach in isotopic labeling to elucidate new structural information on this complex biopolymer. In this project, the structural and dynamic characterization of elastin and elastin peptides will be expanded. The major focus is the structural characterization of isotopically-enriched insoluble elastin from cell culture using solid-state NMR spectroscopy. These studies will be complemented by analogous work on elastin peptides from synthesis and bacterial expression. Finally, investigations of the dynamics in these systems will be pursued. All results will be integrated to provide a comprehensive picture for biological elasticity. The research will involve students at all levels - undergraduate, graduate, and postdoctoral. The research training experience provided herein is cross-disciplinary, exposing students to a range of techniques and expertise, particularly as the project involves several collaborators in elastin biochemistry and matrix biology.