PROTEIN CRYSTALLOGRAPHY AND STRUCTURAL NEUROBIOLOGY

一个通用的策略将探索设计新的蛋白质，自组装成大的对称结构，包括纳米粒子笼，丝，层，和多孔晶体材料。该方法利用天然寡聚蛋白质，以精确的排列进行基因融合。目前的建议是充分探索这一新领域的对称蛋白质设计，我们将验证的方法，并测试其局限性，通过设计和实验表征一系列的组件具有广泛的架构。除了在材料科学中的潜在未来应用之外，这些组装的基本原理将用于阐明和指导一些天然蛋白质组装的实验。基因组学研究将揭示潜在的未知蛋白质复合物，已经通过获得多个寡聚化结构域。感兴趣的候选物的四级结构和对称性将通过生物物理学和晶体学方法进行研究。最后，纤维形成蛋白，如淀粉样蛋白transthyretin，将研究化学交联和EPR方法，看看什么样的作用对称性可能发挥丝状组装。

A general strategy will be explored for designing novel proteins that self- assemble into large symmetrical structures, including nanoparticle cages, filaments, layers, and porous crystalline materials. The method makes use of natural oligomeric proteins, genetically fused in precise arrangement. The present proposal is to fully explore this new area of symmetric protein design we will validate the method and test its limitations by designing and experimentally characterizing a series of assemblies with a wide range of architectures. Beyond the potential future applications in materials science, the principles underlying these assemblies will be used to illuminate and guide experiments on some natural protein assemblies. Genomic studies will uncover potentially uncharacterized protein complexes that have evolved by acquiring multiple oligomerization domains. The quaternary structure and symmetry of interesting candidates will be investigated by biophysical and crystallographic methods. Finally, fiber forming proteins, such as the amyloid protein transthyretin, will be studied by chemical cross-linking and EPR methods to see what role symmetry may play in filamentous assemblies.