Cryptochrome magnetoreception: four tryptophans could be better than three

Abstract

The biophysical mechanism of the magnetic compass sensor in migratory songbirds is thought to involve photo-induced radical pairs formed in cryptochrome (Cry) flavoproteins located in photoreceptor cells in the eyes. In Cry4a—the most likely of the six known avian Crys to have a magnetic sensing function—four radical pair states are formed sequentially by the stepwise transfer of an electron along a chain of four tryptophan residues to the photo-excited flavin. In purified Cry4a from the migratory European robin, the third of these flavin–tryptophan radical pairs is more magnetically sensitive than the fourth, consistent with the smaller separation of the radicals in the former. Here, we explore the idea that these two radical pair states of Cry4a could exist in rapid dynamic equilibrium such that the key magnetic and kinetic properties are weighted averages. 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.

Broadband 75–85 MHz radiofrequency fields disrupt magnetic compass orientation in night-migratory songbirds consistent with a flavin-based radical pair magnetoreceptor

“…Cryptochromes (Cry), currently the only group of vertebrate proteins known to form radical pairs upon photoexcitation (Ritz et al 2000 ; Liedvogel et al 2007 ; Maeda et al 2012 ; Zoltowski et al 2019 ; Xu et al 2021 ), have been proposed as the light-activated, radical-pair-forming, magnetosensory proteins in the avian retina (Ritz et al 2000 ; Mouritsen et al 2004 ; Maeda et al 2012 ; Nießner et al 2014 ; but see Bolte et al 2021 ; Hore and Mouritsen 2016 ; Günther et al 2018 ; Xu et al 2021 ; Wong et al 2021 ). At least six different cryptochrome variants are known to occur in retinal neurons of night-migratory songbirds: Cry1a (Mouritsen et al 2004 ; Möller et al 2004 ; Nießner et al 2011 ; Bolte et al 2021 ), Cry1b (Möller et al 2004 ; Bolte et al 2016 ; Nießner et al 2016 ), Cry2a (Mouritsen et al 2004 ; Möller et al 2004 ; Balay et al 2021 ; Einwich et al 2021 ), Cry2b (Hochstoeger et al 2020 ; Balay et al 2021 ), Cry4a (Liedvogel and Mouritsen 2010 ; Günther et al 2018 ; Wu et al 2020 ; Xu et al 2021 ), and Cry4b (Einwich et al 2020 ); a and b forms are alternative splicing variants.…”

Genetic analysis of cryptochrome in insect magnetosensitivity

“…However, since these studies, the possibility has been raised that there is a fourth terminal Trp (which would be Trp394 in d CRY) that would remain intact in these d CRY mutants ( Muller et al, 2015 ; Nohr et al, 2016 ). However, its role in magnetosensitivity, either as the terminal Trp or as a functional partner to Trp342 remains to be determined ( Muller et al, 2015 ; Nohr et al, 2016 ; Wong et al, 2021 ).…”

Magnetic field effects in biology from the perspective of the radical pair mechanism

“…In cryptochrome-4a, sequentially four radical pair states are formed by the progressive transfer of an electron along a chain of four tryptophan residues to the photo-excited flavin. In a recent study, Hore and co-workers suggest that, based on spin dynamics, while the third radical pair is mainly responsible for magnetic sensing, the fourth could enhance initiation of magnetic signalling particularly if the terminal tryptophan radical can be reduced by a nearby tyrosine (Tyr) 427 . They concluded that this arrangement may play an essential role in sensing and signalling functions of the protein.…”