Date of Award
Doctor of Philosophy (PhD)
Biochemistry & Molecular Biophysics
Recent evidence suggests that birds, insects, and other animals may be able use Earth’s 50 μT magnetic field for navigation. This magnetic sense is hypothesized to be facilitated by an ocular cryptochrome (Cry): a protein containing a flavin adenine dinucleotide (FAD) and a tryptophan (Trp) triad. Upon light activation, electron transfer between the FAD and Trp forms a spin-correlated radical pair, the life time of which has been shown sensitive to mT magnetic fields. However, due to the extreme fragility of cryptochrome, studying biological magneto-sensing, has proven difficult. Currently there is no evidence that cryptochrome can sense fields as weak as Earth’s. In order to overcome these technical challenges and better understand the functional requirements for a molecular compass, we have designed a simple model system; protein maquettes. Maquettes are remarkably simple, stable and absolutely designable, man-made proteins that enable experiments not possible in cryptochrome. Here we present the biophysical characterization of a family of maquettes equipped with flavin and tryptophan. By varying the distances between the cofactors, we can explore their photo-physics and ability to generate a magnetically sensitive radical pair using transient absorption spectroscopy. Despite bearing no structural resemblance to the cryptochrome fold, these maquettes generate a flavin-tryptophan radical pair that demonstrates a magnetic field effect at fields as low as 1 mT. This observation suggests that a flavin-tryptophan radical pair is sufficient for magneto-sensing and may even sense a field as weak as Earth’s. This work offers further proof that cryptochrome could be the biological magneto-sensor opens the door to a multitude of future experiments.
Bialas, Chris, "The Design And Engineering Of An Artificial Protein Magnetosensor" (2017). Publicly Accessible Penn Dissertations. 2192.