Nanoscale Approaches to Understanding Membrane Protein Function

 描述(申请人提供)：生物膜是所有生命形式所必需的。这些脂质双层将细胞内外分开，在高等生物体中，提供内部间隔之间的分离。因此，它们是提供识别和通信的过程的场所，并提供了一系列蛋白质的家，这些蛋白质介导信号、催化、能量的产生和转导以及分子的进出口。尽管膜和膜蛋白在生命中起着核心作用，但通常很难用生物化学和分子生物学的常规工具来研究它们。膜蛋白在脱离其天然脂质环境时表现出丧失或改变的活性。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。纳米盘，由我们实验室发现的两亲性支架蛋白溶解的自组装纳米级脂质双层，使这些领域的新发现成为可能。在该奖项的支持下，我们将进一步开发纳米盘系统，为实现催化、信号和分子识别等机制提供新的生化和生物物理途径。正在研究的复杂大分子组件包括那些参与凝血、异物和激素代谢以及细胞转化/迁移的组件。

 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.