Self Assembled Lipid Icosohedra for Highthroughput Membrane Protein Structure Det

描述(申请人提供)：这项建议旨在通过一种结合高通量电子显微镜单颗粒分析和新的自组装方法的新方法来最大限度地减少膜蛋白结构确定的三个瓶颈。这种方法的验证将通过应用于几种蛋白质的结构分析来实现，这些蛋白质代表了具有生物医学重要性的主要类别的真核膜蛋白。这项提议的总体目标将是确定它们的结构，同时充分开发这一方法，以解决我们自己和其他实验室中更多的膜蛋白靶标。已知的大多数人类药物靶标是膜蛋白，未来基于结构的药物设计工作的成功将严重依赖于膜蛋白结构信息。这一建议将最大限度地减少膜蛋白结构测定的三个瓶颈，将高通量电子显微镜单颗粒分析与新的自组装方法相结合。该项目的成功将降低获得基于结构的药物设计所需信息的障碍，从而继续进行广泛的疾病。

DESCRIPTION (provided by applicant): This proposal aims to minimize the three bottlenecks of membrane proteins structure determination with a novel approach that combines high throughput electron microscopy single particle analysis with a novel self-assembling method. Validation of this approach will be realized by application to the structural analysis of several proteins which represent major categories of eukaryotic membrane proteins of biomedical importance. The overall objective of this proposal will be determining their structures and to simultaneously fully develop this approach to tackle further membrane protein targets in our own and other laboratories. The majority of known human pharmaceutical targets are membrane proteins and the future success of structure based drug design efforts will rely heavily on membrane protein structural information. This proposal will minimize the three bottlenecks of membrane proteins structure determination with a novel approach that combines high throughput electron microscopy single particle analysis with a novel self-assembling method. The success of this project will lower the barrier for obtaining the needed information for structure based drug design to proceed for a wide range of diseases.