PROTEIN CRYSTALLOGRAPHY AND STRUCTURAL NEUROBIOLOGY

我们将探索设计一种自组装成大型对称结构的新型蛋白质的一般策略，包括纳米粒子笼、细丝、层和多孔晶体材料。该方法利用天然寡聚蛋白，基因融合在精确的排列。目前的建议是充分探索对称蛋白质设计的这个新领域，我们将通过设计和实验表征一系列具有广泛结构的组装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之外，这些组合的基本原理将用于照亮和指导一些天然蛋白质组合的实验。基因组研究将揭示通过获得多个寡聚化结构域而进化的潜在未表征的蛋白质复合物。我们将用生物物理和晶体学的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发挥的作用。

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.