Nanoscale Approaches to Understanding Membrane Protein Function

了解膜蛋白功能的纳米方法

• 批准号: 9276726
• 负责人: STEPHEN G. SLIGAR
• 金额: $ 67.73万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9276726
• 关键词: Architecture; Award; Biochemical; Biological; Biophysics; Blood coagulation; Catalysis; Cells; Communication; Complex; Development; Environment; Enzymatic Biochemistry; Event; Generations; Home environment; Investigation; Laboratories; Life; Lipid Bilayers; Lipids; Macromolecular Complexes; Mediating; Membrane; Membrane Proteins; Methodology; Molecular Biology; Organism; Process; Proteins; Role; Scaffolding Protein; Signal Transduction; Site; Surface; System; Xenobiotic Metabolism; biochemical tools; cell transformation; hormone metabolism; macromolecular assembly; migration; molecular recognition; nanodisk; nanoscale; novel; protein function; public health relevance

 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.

 描述（由申请人提供）：所有生命形式都需要生物膜，这些脂质双层将细胞的内部和外部分开，并且在高等生物体中提供内部区室之间的分隔，因此，它们是进行过程的场所。尽管膜和膜蛋白在生命中发挥着核心作用，但它提供识别和通讯，并为介导信号传导、催化、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了家园。研究使用生物化学和分子生物学的正常工具当从其天然脂质环境中去除时，其活性会丧失或改变。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。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，在这些领域取得了新的发现，在该奖项的支持下，我们将进一步开发 Nanodisc 系统，以实现这些领域的新发现。为实现催化、信号传导和分子识别所涉及的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/迁移的组装体。