UC San Diego

Protein-protein interactions are ubiquitous throughout nature at many length and time scales—from transient interactions between individual proteins for signaling and electron transfer to the self-assembly over large distances of bacterial S-layer protein coats. Extensive research has been undertaken to attempt to mimic, interrogate, interrupt, or design protein-protein interactions, but natural protein-protein interactions often form as a result of many accumulated weak interactions over large, heterogeneous molecular surfaces, making them challenging to design. As a way to overcome these challenges, we have previously introduced methods of synthesizing protein-protein interactions with minimal surface design through the directional and highly controllable coordination of metal ions on protein surfaces.

The goal of this thesis work has been to expand the scope and functionality of these metal-directed protein and peptide interactions. First, we show that, like proteins, short peptides can be directed to fold and assemble in biologically relevant ways using coordination chemistry, while incorporating additional metal-based functionality on the peptide backbone. We then extend the scale of protein self-assembly to highly ordered, crystalline protein nanotubes with tunable diameters. Finally, we demonstrate the ability to assemble protein-DNA nanomaterials in a manner that, similar to what is observed in nature, relies on the sum of a number of weak interactions to form highly ordered protein-DNA arrays. Overall, we demonstrate the ability to use metal ions to coordinate interactions on scales as small as single protein-protein interactions to as large as micrometer scale arrays.

Here, we have expanded the functionality of these metal-directed protein and peptide interactions. First, we show that peptides can be directed to fold and assemble in biologically relevant ways using coordination chemistry, while incorporating additional metal-based functionality on the peptide backbone. We then extend the scale of assembly to highly ordered, crystalline protein nanotubes with tunable diameters. Finally, we demonstrate the ability to assemble protein-DNA nanomaterials in a manner that, similar to what is observed in nature, relies on the sum of a number of weak interactions to form highly ordered protein-DNA arrays. Overall, we demonstrate the ability to use metal ions to coordinate interactions on scales as small as single protein-protein interactions to as large as micrometer scale arrays.