Franziska Thomas's Research Page

Current work

My work is focused on the design and synthesis of switchable synthetic proteins. I intend to combine the coiled coil motif with functional metal-responsive folding motifs. In this way, I propose to create novel hybrid peptide folds, which will change their conformation in the presence of a metal. The synthesis of such multi-domain compounds will be achieved by native chemical ligation and similar techniques.

As a proof-of-concept design I chose a helix-zinc finger-helix protein. In the absence of zinc the region encoding the zinc finger motif will be disordered and the two alpha-helices will associate to form an antiparallel coiled coil. The addition of zinc is supposed to trigger the folding of the zinc finger motif. The C-terminal helix of the zinc-finger is flush with the second coiled-coil helix. Thus, zinc binding is proposed to induce a conformational switch resulting in an open structure displaying unpaired amphipathic helices. Intermolecular formation of parallel coiled coils from the unpaired helices will then initiate the growth of a protein fibre.

The helix-zinc finger-helix protein will be the basis for the design of further proteins and protein materials with different properties like metal-responsiveness, DNA-binding and protein-binding.