Unraveling the Mechanism of Magnetoreception: Inspecting the Electron Transfer Cascade in Cryptochrome

Magnetoreception plays a key role in the migration of the European robin. Cryptochrome (Cry) is believed to be responsible for the ability of these birds to detect the direction of the geomagnetic field during migration. A cofactor of cryptochrome, flavin adenine dinucleotide (FAD) absorbs blue light, resulting in a ᴨ to ᴨ* transition. In this ᴨ* excited state, FAD is the recipient of four consecutive electron transfers along a tryptophan (Trp) tetrad, which results in a long-lived, spin-correlated, radical-ion pair [FAD͘^– Trp͘⁺]. Spin states of recombination products from radical-ion pairs have been shown to be influenced by weak external magnetic fields, providing the basis for this compass-like magnetoreception mechanism. Recently, expression of the cryptochrome protein found in the European robin (ErCry4a) has been demonstrated. In order to study the involvement of the Trp tetrad in this mechanism, each of the Trp residues was replaced with redox-inactive phenylalanine. Each of these four mutants were compared to the wild-type ErCry4a experimentally using ultrafast transient absorption spectroscopy. Electron transfer times were compared theoretically using QM/MM and the density functional tight-binding approach. Current discourse in the field includes the number of Trp residues involved in the electron transfer chain and the role of Cry in the overall magnetoreception signaling cascade.