Metal-Directed Protein Self-Assembly and Construction of Selective Metal Binding Sites in Protein-Protein Interfaces

该奖项是根据2009年《美国复苏和再投资法案》(公法111-5)提供资金的。无机化学、生物无机化学和金属有机化学项目的这一研究奖支持加州大学圣地亚哥分校的F.Akif Tezcan教授开展由金属配位指导的超分子蛋白质结构自组装的基础/基础研究。大自然使用蛋白质作为复杂纳米结构的主要构建块，这些结构执行复杂的任务和化学转换。然而，多蛋白质复合体的合理组装是一个尚未满足的挑战，因为蛋白质-蛋白质相互作用包括一组广泛的弱、非共价键，这些键对于从头设计来说是困难的目标。在这个研究计划中，利用金属-配体相互作用的强度、方向性和选择性来控制蛋白质-蛋白质相互作用，从而在不需要广泛和互补的结合表面的情况下实现特异性和亲和力。这种蛋白质-蛋白质相互作用的无机化学控制最终被用于构建基于蛋白质的功能性生物组装和建立在蛋白质-蛋白质界面上的新型金属分配中心。这一跨学科计划提供了一个有效的平台，吸引代表人数不足的群体的成员从事研究工作，指导和招募那些特别难适应大型研究型大学的严格要求的转学学生，并扩大到当地高中的学生。该奖项下的研究将为下一代具有反应性界面金属中心的稳定、多孔的蛋白质框架铺平道路，这些生物材料的组装/拆卸可以受到外部刺激的控制，并提供关于天然金属蛋白和酶的进化的基本信息。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). This Research award in the Inorganic, Bioinorganic and Organometallic Chemistry program supports work by Professor F. Akif Tezcan at the University of California, San Diego to carry out fundamental/basic studies on the self-assembly of supramolecular protein architectures directed by metal coordination. Nature uses Proteins as premier building blocks for sophisticated nanoscale architectures that carry out complex tasks and chemical transformations. Yet, the rational assembly of multi-protein complexes is an unmet challenge, because protein-protein interactions comprise an extensive set of weak, non-covalent bonds that are difficult targets for de novo design. In this research program, the strength, directionality and selectivity of metal-ligand interactions are exploited to control protein-protein interactions, thereby achieving specificity and affinity without requiring extensive and complementary binding surfaces. Such inorganic chemical control of protein-protein interactions is ultimately utilized towards the construction of functional, protein-based bioassemblies and novel metallocenters built within protein-protein interfaces. This trans-disciplinary program provides an effective platform for attracting members of underrepresented groups to research careers, mentoring and recruitment of transfer students who have a particularly hard time to adjust to the rigors of a large research university, and outreach to students in local high schools.The research under this award will pave the way for the future generation of stable, porous protein frameworks with reactive interfacial metal centers, biomaterials whose assembly/disassembly can be controlled by external stimuli, and provide fundamental information regarding the evolution of natural metalloproteins and enzymes.