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

金属介导的蛋白质-蛋白质相互作用作为新型生物材料的基础

• 批准号: 7880823
• 负责人: Eric Nolan Salgado
• 金额: $ 3.19万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7880823
• 关键词: 3-Dimensional; Affinity; Amino Acids; Binding; Biochemical; Biocompatible Materials; Catalysis; Cell physiology; Chemicals; Complement; Computer Simulation; Computing Methodologies; Contrast Media; Cysteine; Cytochromes; Development; Diagnostic; Drug Delivery Systems; Engineering; Environment; Generations; Goals; Guidelines; Ions; Lead; Ligands; Magnetic Resonance Imaging; Mediating; Medical; Membrane Proteins; Metals; Methods; Modeling; Molecular; Morphology; Organism; Play; Property; Proteins; Role; Side; Site-Directed Mutagenesis; Specificity; Structure; Surface; Techniques; Therapeutic; Thermodynamics; Variant; Work; base; biological systems; crosslink; design; disulfide bond; in vivo; novel; preference; programs; protein protein interaction; self assembly; sensor; tool

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.

描述（由申请人提供）：蛋白质-蛋白质相互作用实际上决定了每一个细胞过程，因此，控制它们的能力可用于探测细胞网络，并提供一种创造新的基于蛋白质的材料的方法。虽然被广泛研究，但蛋白质-蛋白质相互作用的物理基础还没有得到很好的理解，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，我的工作试图采用金属配位基序放置在非自我相互作用的蛋白质的表面，以诱导它们的协会通过引入特定的金属离子。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，我们的目标是生成金属介导的蛋白质-蛋白质相互作用的一般设计原则。我们建议，这些设计原则可以用于许多螺旋蛋白，其协会在生物系统中起着至关重要的作用。与金属介导的蛋白质-蛋白质相互作用的准则的发展相一致，计算建模和生物化学技术的组合将用于金属诱导的蛋白质组装体的稳定。这种稳定性的提高将允许这些组件功能化以用于生物材料应用。预期功能性多蛋白质组装体的应用包括但不限于它们作为体内和离体金属传感器、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。这项工作的目的是通过开发蛋白质-蛋白质相互作用的设计原理来获得这种控制，这种相互作用可以通过添加金属离子来选择性地诱导。这种金属介导的蛋白质相互作用还将用于指导蛋白质自组装，以构建2-D和3-D蛋白质基材料，其应用范围从医学诊断和治疗药物递送到催化。