The ferritin family of iron-storage proteins is remarkable for its conserved quaternary structure throughout animals and bacteria.  Twenty-four 4-helix bundle protein subunits self assembl to form a very stable 8-nm diameter cavity protein (figures below) that can bind thousands of iron atoms.  We have demonstrated recently the ability to template the synthesis of homogeneous, biocompatible gold and silver nanoparticles inside the ferritin shell.  We are currently exploiting many properties of these ferritin nanoparticles for the creation of biosensors and conducting nanomaterials.

One goal of this project is to engineer novel ferritin proteins that have been optimized for binding to transition metals.  Computational studies are being done in collaboration with Prof. Jeffery Saven’s group, also in the UPenn Chemistry Department.  In one example of ferritin re-design, we generated the largest hydrophobic cavities ever seen in a protein.  Incorporating large hydrophobic cavities into proteins is typically energetically unfavorable, and the Saven algorithms provide a statistical method for optimizing the stability and inter-subunit helical interactions of Dps and ferritin.  To date, we have generated approximately 10 Dps mutants in E. coli.  Many of these proteins have near wild-type stability.  We are in the process of designing ferritin nanocavities for nanoparticle synthesis and unique chemical reactions.