Nature utilizes self-assembly to build functional structures from bio-macromolecules. In synthetic systems, self-assembly is an attractive tool to manipulate polypeptides into supramolecular structures at physiologically relevant conditions. Naturally derived protein motifs present useful self-assembling properties, and combination of multiple motifs can provide new opportunities to control the assembly processes. For example, elastin-like polypeptides (ELPs) are temperature-responsive self-assembling protein motifs, which have been extensively engineered to form various suprastructures upon inverse phase transition. Leucine zippers are coiled coil peptides that form dimeric or higher ordered complexes with engineered affinity. This work illustrates how engineered protein building blocks containing these domains can form different structures dictated by assembly conditions. More importantly, the protein building blocks also contain folded, globular proteins and these are incorporated into the structures without disruption of folding and activity. Two examples of such structures will be discussed, protein vesicles and protein nanosheets. Protein vesicles are formed when a globular protein and ELP are attached non-covalently via leucine zippers and warmed to room temperature in buffer. The vesicles are hollow or can encapsulate small molecules, protein coacervates, or nanoparticles. Their size and formation is salt dependent. Protein nanosheets are formed when random coil polypeptides capped with leucine zippers are dried on a surface. Rehydration of the sheets in the presence of globular proteins fused to leucine zippers integrates the proteins on the sheets. For both structures, these are the first examples of their kind that contain full-sized, folded globular proteins. Incorporation of various types of proteins including enzymes, therapeutic proteins, or binding ligands can lead to significant benefits in applications such as biocatalysis, drug delivery, and molecular imaging.

Supramolecular polypeptide structures assembled from folded, globular proteins

249th National Meeting (2015)

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