Team:UCLA/Projects/Protein Cages

iGEM UCLA




Protein Cages

Proteins naturally have evolved to self-assemble into supramolecular structures often playing a role in complex cellular functions. These supramolecular structures are built mostly by copies of the same protein subunit and are arranged in a symmetric fashion through non-covalent bonding. Though we see these in nature through specific proteins, what if we were able to engineer our own protein subunits and create complex structures for our own applications?

A proven way to form these supramolecular structures is to engineer a self-assembling protein molecule as a fusion of two different, naturally oligomeric protein domains. In order to get a pre-defined, homogenous structure, the two components must be fused in a way that follows specific angular rules. To satisfy this requirement, the two proteins fused are required to have terminal alpha helices and are attached by an alpha helix preferring molecule. This allows the fused protein subunit to be sturdy without variance in its bond angles and allows us to predict with more accuracy on how the structure is going to form. This technique has worked and the predicted cage-like structure was achieved through a 12 subunit assembly.

What can we do with such a cage? The most obvious application that comes to mind is drug delivery. We might be able to engineer a protease induced cleavage cite onto our cage making it an efficient delivery system where the cage breaks open the moment it comes in contact with its inducer and releases the drug. This technology can even lead to formation of protein cages made up of human proteins with non-immunogenic properties. Such a cage would have an immense impact in field of drug delivery and in the field of medicine as a whole.