PROTEIN CRYSTALLOGRAPHY AND STRUCTURAL NEUROBIOLOGY

将探索设计新型蛋白质的一般策略，这些蛋白质自组装成大型对称结构，包括纳米颗粒笼子、细丝、层和多孔性晶体材料。该方法利用天然寡聚蛋白，在基因上精确排列融合。目前的提议是为了充分探索这一对称蛋白质设计的新领域，我们将通过设计和实验表征一系列具有广泛结构的组件来验证该方法并测试其局限性。除了在材料科学中潜在的未来应用，这些组件背后的原理将被用来阐明和指导一些天然蛋白质组件的实验。基因组研究将揭示潜在的未知蛋白质复合体，这些复合体是通过获得多个寡聚化结构域而进化出来的。将用生物物理和结晶学方法研究感兴趣的候选化合物的四元结构和对称性。最后，纤维形成蛋白，如淀粉样蛋白转甲状腺素，将通过化学交联和EPR方法进行研究，以了解对称性在丝状组装中可能扮演的角色。

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.