The design of novel proteins offers unprecedented advantages for human health, such as improved vaccines, drug delivery and novel therapies (e.g. a flu inhibitor, treatment of Alzheimer’s). The state of the art of self-assembling protein nanomaterials is based on the design of protein-protein interfaces. However, due to the complex interplay of numerous weak interactions at the interface the success rate of designed assemblies is currently below 10%.
This proposal aims to increase the success rate of designing large protein assemblies, by using coiled-coils (CC) at the interface. CCs are some of the best understood protein motifs and can be designed with high success rates (>50%). A set of well-defined building blocks (CC-LEGOs) will be created by rigidly fusing CC bundles and natural oligomerization domains.
Due to precise control of crossing angles enabled by the rigid fusion we expect that CC-LEGO structures will have the high design success rate and high solution homogeneity needed for further applications. A toolbox of CC-LEGO blocks will be designed and experimentally tested, capable of forming cages (tetrahedra, cubes, dodecahedra) as well as 1D fibres.
Another important impact of the project is the transfer the protein design know-how from the University of Washington to the Slovenian and regional research ecosystem, increasing its excellence.