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.
| Salgado, Eric N; Radford, Robert J; Tezcan, F Akif (2010) Metal-directed protein self-assembly. Acc Chem Res 43:661-72 |
| Brodin, Jeffrey D; Medina-Morales, Annette; Ni, Thomas et al. (2010) Evolution of metal selectivity in templated protein interfaces. J Am Chem Soc 132:8610-7 |
