Self Assembled Lipid Icosohedra for Highthroughput Membrane Protein Structure Det

描述（由申请人提供）：本提案旨在通过结合高通量电子显微镜单颗粒分析和新型自组装方法的新方法，最大限度地减少膜蛋白结构测定的三个瓶颈。该方法的验证将通过应用于几种蛋白质的结构分析来实现，这些蛋白质代表了生物医学上重要的真核膜蛋白的主要类别。本提案的总体目标将是确定它们的结构，并同时在我们自己和其他实验室中充分发展这种方法来解决进一步的膜蛋白目标。大多数已知的人类药物靶点是膜蛋白，未来基于结构的药物设计工作的成功将在很大程度上依赖于膜蛋白的结构信息。该建议将结合高通量电子显微镜单粒子分析和新颖的自组装方法的新方法最大限度地减少膜蛋白结构测定的三个瓶颈。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，以进行广泛的疾病。

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.