Exploring the Magnetic Field Effect Mechanism in Blue-Light Receptor Proteins: The Physics Behind Magnetoreception

The physical mechanism by which some migratory birds detect the earth’s magnetic field, magnetoreception, has proven to be an intriguing and puzzling problem. The radical pair mechanism, whilst controversial at the time, was proposed by Schulten et al. as a possible mechanism in 1978.1 Since then, a myriad of theoretical and behavioural studies have supported this hypothesis, which has emerged as a front runner for magnetoreception. In particular, a radical pair forming protein, cryptochrome-4a, was discovered in the retina of migratory birds and has been shown to form spin-correlated radical pairs whose subsequent, in vitro, photochemistry are sensitive to magnetic fields.2 However, the role played by amino acid residues adjacent to the tryptophan tetrad responsible for the electron transfer reactions that form radical pairs has been less well studied. The work discussed here explores the radical pairs formed in cryptochrome-4a from a non-migratory bird, the domestic chicken (Gallus gallus), via a combination of electron paramagnetic resonance, transient absorption spectroscopy, optical-cavity spectroscopy and simulations. A detailed comparison between the wild-type protein and three single-point mutants is presented and reveals that amino acids adjacent to the tryptophan tetrad have a negligible role in the development of magnetic field effects. Conversely, shortening the tetrad by single-point mutation has a dramatic impact on the photochemistry and increases the magnetic sensitivity of the protein. The implications of this enhanced sensitivity are discussed with reference to calculations that indicate the enhancement may be reversed in vivo. The results presented show that migratory birds may not have evolutionarily optimised their proteins for magnetic field sensitivity over non-migratory species. Instead, future research must look elsewhere, such as signal transduction, to find the evolutionary origin of the magnetic sense in migratory birds.

1.Schulten, K., Swenberg, C. & Weller, A. A Biomagnetic Sensory Mechanism Based on Magnetic Field Modulated Coherent Electron Spin Motion. Zeitschrift für Physikalische Chemie 111, 1-5 (1978).

2. Xu, J. et al. Magnetic sensitivity of cryptochrome 4 from a migratory songbird. Nature 594, 535–540 (2021).