Nanoscale Approaches to Understanding Membrane Protein Function

 描述（由申请人提供）：生物膜是所有生命形式所需要的。这些脂质双层将细胞的内部和外部分隔开，并且在高等生物中，提供内部隔室之间的分隔。因此，它们是提供识别和通信的过程的场所，并为介导信号传导、催化以及能量的产生和转导以及分子的输入和输出的许多蛋白质提供家园。尽管膜和膜蛋白在生命中扮演着重要的角色，但使用生物化学和分子生物学的常规工具来研究膜和膜蛋白往往很困难。膜蛋白显示损失或改变活动时，从他们的天然脂质环境。同样，揭示在膜表面形成复杂的多组分结构所涉及的基本分子识别事件需要新的方法。纳米圆盘，自组装的纳米级脂质双层溶解的两亲性支架蛋白在我们的实验室中发现，已成为使新的发现在这些领域。在该奖项的支持下，我们将进一步开发Nanodisc系统，为实现催化，信号传导和分子识别机制提供新的生物化学和生物物理路径。研究中的复杂大分子组装体包括涉及血液凝固、异生物质和激素代谢以及细胞转化/迁移的那些。

 DESCRIPTION (provided by applicant): Biological membranes are needed by all life forms. These lipid bilayers separate the inside and outside of the cell and, in higher organisms, provide the separation between internal compartments. As such, they are the site for processes of that provide recognition and communication and provide the home to a host of proteins that mediate signaling, catalysis and the generation and transduction of energy and the import and export of molecules. Despite this central role in life, membranes and membrane proteins have often been difficult to study using the normal tools of biochemistry and molecular biology. Membrane proteins display loss or altered activity when removed from their native lipid environment. Likewise, revealing the fundamental molecular recognition events involved in forming complex multi-component architectures at the membrane surface requires new methodologies. Nanodiscs, self-assembled nanoscale lipid bilayers solubilized by an amphipathic scaffold protein discovered in our laboratory, have served to enable new discoveries in these arenas. Under support from this award, we will further develop the Nanodisc system to provide novel biochemical and biophysical paths to the realization of the mechanisms involved in catalysis, signaling and molecular recognition. Complex macromolecular assemblies under investigation include those involved in blood coagulation, xenobiotic and hormone metabolism and cell transformation/migration.