Metal-mediated Protein-protein Interactions as Basis for Novel Bio-materials

描述(申请人提供)：蛋白质-蛋白质相互作用几乎决定了每一个细胞过程，因此，控制它们的能力可以用来探测细胞网络，并提供一种创造新的蛋白质材料的方法。虽然被广泛研究，但蛋白质-蛋白质相互作用的物理基础还不是很清楚，因为它们涉及包含许多弱相互作用的大分子表面。为了避免这些并发症，我的工作试图利用放置在非自相互作用蛋白质表面的金属配位基序，通过引入特定的金属离子来诱导它们的结合。基于对一系列具有不同金属配位基序的不同蛋白质变体的分析，我们的目标是产生金属介导的蛋白质-蛋白质相互作用的一般设计原则。我们认为这些设计原则可以应用于许多螺旋蛋白质，它们的结合在生物系统中起着至关重要的作用。随着金属介导的蛋白质-蛋白质相互作用指南的制定，将结合计算建模和生化技术来稳定金属诱导的蛋白质组装。这种增加的稳定性将允许生物材料应用的这些组件的功能化。功能性多蛋白质组装体的应用有望包括但不限于，它们作为体内和体外金属传感器、磁共振成像(MRI)造影剂和药物递送剂的用途。在生命系统中，以合理的方式控制特定蛋白质-蛋白质相互作用的能力将是理解正常细胞过程和疾病状态的有力工具。这项工作旨在通过开发蛋白质-蛋白质相互作用的设计原则来获得这种控制，这种相互作用可以通过添加金属离子选择性地诱导。这种金属介导的蛋白质相互作用也将有助于将蛋白质自组装引导到构建基于2-D和3-D蛋白质的材料，其应用范围从医学诊断和治疗性药物输送到催化。

DESCRIPTION (provided by applicant): Protein-protein interactions dictate virtually every cellular process and, therefore, the ability to control them can be used to probe cellular networks and provide a means for creating new, protein-based materials. Though extensively studied, the physical basis for protein-protein interactions is not well understood due to fact that they involve large molecular surfaces that comprise many weak interactions. In order circumvent these complications, my work seeks to employ metal coordination motifs placed on the surfaces of non-self-interacting proteins, in order to induce their association through introduction of specific metal ions. Based on analysis of an array of different protein variants with a diverse set of metal coordination motifs, we aim to generate general design principles for metal-mediated protein-protein interactions. We propose that these design principles can be employed for many helical proteins, whose association plays crucial roles in biological systems. Coincident with the development of guidelines for metal-mediated protein-protein interactions, a combination of computational modeling and biochemical techniques will be employed for the stabilization of the metal-induced protein assemblies. This increased stability will allow for the functionalization of these assemblies for biomaterials applications. The applications of functional multi-protein assemblies are expected to include, but are not limited to, their use as in vivo and ex vivo metal sensors, magnetic resonance imaging (MRI) contrasting agents, and drug delivery agents. Within living systems, the ability to control specific protein-protein interactions in a rational manner would be a powerful tool for understanding both normal cellular processes and diseased states. This work aims to gain such control by developing design principles for protein-protein interactions that can be selectively induced by the addition of metal ions. Such metal-mediated protein interactions will also serve to direct protein self-assembly toward building 2- and 3-D protein-based materials, whose applications range from medical diagnostics and therapeutic drug delivery to catalysis.