Cryptochrome magnetoreception: four tryptophans could be better than three
Journal of the Royal Society Interface
The biophysical mechanism of the magnetic compass sensor in migratory songbirds is thought to involve photo-induced radical pairs formed incryptochrome (Cry) flavoproteins located in photoreceptor cells in the eyes. In Cry4aâthe most likely of the six known avian Crys to have a magneticsensing functionâfour radical pair states are formed sequentially by the stepwise transfer of an electron along a chain of four tryptophan residuesto the photo-excited flavin. In purified Cry4a from the migratory European robin, the third of these flavinâtryptophan radical pairs is moremagnetically sensitive than the fourth, consistent with the smaller separation of the radicals in the former. Here, we explore the idea thatthese two radical pair states of Cry4a could exist in rapid dynamic equilibrium such that the key magnetic and kinetic properties are weightedaverages. Spin dynamics simulations suggest that the third radical pair is largely responsible for magnetic sensing while the fourth may be better placed to initiate magnetic signalling particularly if the terminal tryptophan radical can be reduced by a nearby tyrosine. Such an arrangement could have allowed independent optimization of the essential sensing and signalling functions of the protein. It might also rationalize why avian Cry4a has four tryptophans while Crys from plants have only three.