Birds use the magnetic field of the Earth to navigate during their annual migratory travel. The possible mechanism to explain the biophysics of this compass sense involves electron transfers within the photoreceptive protein cryptochrome. How the information about the magnetic field is passed on from cryptochrome, however, is still unknown, since it remains to be shown which other proteins or other molecules that may interact with cryptochrome.
You can read more about the avian magnetic compass here.
The ISCA1 complex
A study [Qin et al., 2016] claimed that the sensitivity to changes in the magnetic field is enhanced by a coupling to an iron rich polymer complex which couples to multiple cryptochromes. For the iron sulphur clusters to participate in the compass sense, they either need to donate an electron to a specific tryptophane in the cryptochome or accept an electron from the flavin adenine dinucleotide (FAD) co-factor in the cryptochrome. To validate the claim, it is needed to independently reconstruct this complex and describe its interaction with Drosophila melanogaster cryptochromes. The polymer complex consists of iron sulphur containing assembly ISCA1 protein monomers with internally bound iron sulphur clusters and simultaneously binds ten cryptochromes, shown in Fig. 1. Homology modelling and crystal packing structure of the used proteins is used to construct the large cryptochrome-ISCA1 complex, which reveals that the iron sulphur clusters are too far away to participate in any electron transfer whatsoever.
The dynamic behaviour of the cryptochrome-ISCA1 complex is monitored to investigate both the time-evolution of the distance between the co-factors involved in electron transfer, and the interaction energy between cryptchrome and ISCA1, to see if the cryptochromes stick to ISCA1 and if they do so consistently along the rod. As seen in Fig. 2, the interaction energy is non-homologues along the ISCA1-rod it, revealing that the complex does likely not exist in the proposed form, and the large distance between the cofactors participating in electron factors rules out that this cryptochrome interaction has any relevance to magnetoreception. A more interesting interaction partner to cryptochrome is still sought after.
Can ascorbate play a role?
It was proposed in [Alpha A. Lee et al.; J. R. Soc. Interface, 11, 20131063 (2014)] that perhaps ascorbate, the ionic form of ascorbic acid (vitamin C), might be involved in magnetoreception, if this small molecule could get close enough to the surface-exposed tryptophan radical that is present in cryptochrome after photoactivation, and transfer an electron - leading to a radical pair between FAD and ascorbate instead. The central question in the ascorbate hypothesis is, therefore, whether the electron transfer from ascorbate to the tryptophan radical can happen.
Ascorbate was proposed to be involved in magnetoreception because its radical form has very small hyperfine interactions, i.e. very little coupling between the unpaired electronic spin and the spins of magnetic nuclei in ascorbate. Having small hyperfine interactions was shown to be desirable for one of the radicals in a radical pair, when paired with an FAD radical, since such a radical pair was shown to have a high sensitivity to the geomagnetic field - much more sensitive than an FAD/Tryptophan radical pair.
It was shown in [Nielsen et al.; J. R. Soc. Interface, 2017] using molecular dynamics simulations that ascorbate ions can indeed get close, and bind near the tryptophan radical as illustrated in Fig. 3. Furthermore the binding time of ascorbate was studied through a large set of additional simulations, and turned out to be about 1 ns as illustrated in Fig. 4.
At the same time it was shown, however, that the expected electron transfer from ascorbate to the tryptophan radical appears to be much too slow to have any impact, and it was therefore concluded that ascorbate is unlikely to play any role in magnetoreception unless exceptionally high ascorbate concentrations are found within the cryptochrome-containing cells.