(324j) Exploration of a Protein Molecular Carrier: Self-Assembly and Stability

The precision of natural protein nanostructures is remarkable, and they can be used as scaffolds upon which to build new functionalities. We are investigating the use of genetically-engineered protein assemblies as carriers for pharmaceutically-active molecules. Our model system is the E2 component of pyruvate dehydrogenase, a protein complex that naturally self-assembles to form a 25-nm hollow spherical complex in which guest molecules potentially can be encapsulated. Examination of the self-assembly characteristics through site-directed mutagenesis has revealed the system's robustness with respect to changes in the internal cavity. The system maintains its molecular structure upon incubation at high temperature as well as various solvents. This property is important for establishing the scaffold's potential as a molecular carrier in targeted drug delivery.