Abstract
Qin et al. (A magnetic protein compass, Nature Materials 15, 217-226, 2016) claim that "MagR is the first known protein that carries an intrinsic magnetic moment at ambient temperature". We show here that the claim must, unfortunately, be fundamentally wrong.
Qin et al. 2015 [1] present a highly innovative strategy for finding interaction partners with the candidate magnetosensory protein cryptochrome (Cry). They rename IscA1 as MagR and present it as a putative interaction partner of Cry4, which in itself will be a truly exciting result if confirmed by other research groups. Yet, we have difficulties in comprehending at least three of the key claims in the paper: (a) That the iron-sulfur cluster protein would be so strongly magnetic at room temperature that it aligns with the Earth’s magnetic field; (b) that the interaction partner for Cry should be a strongly magnetic entity; and (c) that a magnetoreceptive Cry4 should be located in many different cell types within the retina.
To (a): The magnetization curve data (Fig. 5e and Supp. Fig. 16 of [1]] suggests a very small protein magnetization, below 10-3 emu/g in a magnetic field of H=100 Oe (10 mT). A magnetization of 10−3 emu/g translates into a magnetic dipole moment mp of less than 1 μB (Bohr magneton, i.e., the magnetic moment of a single spin) per Cry4-MagR complex consisting of 20 MagR and 10 Cry units with a total molecular weight of about 840 kDa. Consequently, the magnetic moment of the Isca1-Cry4 complex would according to the measurements of Qin et al.’s [1] own data on average be smaller than that of a free radical (for details, see supplement). Furthermore, for mp=1 μB at H=0.5 Oe, the magnetic energy is ten million times smaller than the thermal energy at room temperature, which would imply a random distribution in an orientation experiment as shown in Fig. 5a of [1). In contrast, as shown in SI Material here, to produce the distribution of long axes shown in Fig. 5b of [1], the magnetic moment mp would have to be seven orders of magnitude higher than the value determined from the magnetization curves. Therefore, the alignment obtained in [1] must be an artifact due to some systematic bias.
We also find it hard to understand from a theoretical point of view how the claimed ferrimagnetic properties with a stable magnetic polarity at room temperature could possibly emerge in the Cry4-MagR-polymer protein complex, all the more so because electron spin resonance and Mössbauer spectroscopy have shown iron-sulfur cluster proteins to be either diamagnetic or paramagnetic [2] and that there is only one known class of organometallic magnets in which room temperature ferrimagnetism exists: the polymer ferrimagnet VII[TCNE]x (TCNE=tetracyanoethylene, x≈2) and its analogs [3]. Compared to the Cry4-MagR complex, the VII[TCNE]x and related designer magnets have abundant paramagnetic centers that are bridged in a three-dimensional network structure by cyanide ligands that mediate strong antiferromagnetic coupling between the paramagnetic centers of different spin quantum numbers and thereby cause ferrimagnetism [4]. Such a strong and three-dimensional coupling of spins is a key requirement for a high ordering temperature (i.e., room-temperature ferri/ferromagnetism). In contrast, the Cry4-MagR complex (structure shown in Fig. 3 of [1]) with its sparse iron centers obviously lacks this requirement: The few “iron loops” are too isolated in the structure, i.e., too far away from adjacent iron loops to be significantly exchange coupled. The only strong exchange coupling present in the system is within a single [2Fe-2S] cluster, which is of antiferromagnetic nature (superexchange via sulfide bridge) and couples the 2 Fe spins antiparallel to each other, resulting either in net spin, S=0 (diamagnetic, if both Fe have the same valence), or a net paramagnetic spin s=1/2 (just like a free radical) in the mixed valence system [FeIIIFeII-2S], see [2]). Exchange interactions among paramagnetic [2Fe-2S] clusters of adjacent IscA1 units will be weak (i.e., dipolar-dipolar coupling instead of orbital overlap) and may lead to spontaneous magnetization below a few Kelvin, but no spontaneous magnetization at anywhere near room temperature.
To us, therefore, contamination rather than intrinsic protein magnetism seems to be the only plausible reason why the protein crystals were observed to spin in a rotating magnetic field. Although the light-microscopy based technique used does not yield false positives (because an object spinning coherently with the magnetic field must be magnetic], it requires further transmission electron microscopic analysis to rule out contamination artifacts [5].
To (b): The radical-pair mechanism does not require a magnetic protein partner to work [6], and if an interaction partner of Cry were so strongly magnetic that it aligns to the Earth's magnetic field, there would be no need for Cry as a magnetoreceptor. Of course, it is possible that not Cry4, but MagR is the magnetoreceptor and that Cry4 would only be a non-magnetically sensitive part of the signaling transduction cascade. However, that possibility is in poor agreement with several other results in the field such as the high sensitivity to radio-frequency magnetic fields observed in migratory birds [7].
To (c): The Cry4 and IscA1 stainings in Figure 4 of [1] basically report that both proteins are located in more or less all cells in the retina, and we suspect that they would be found in most cells in the rest of the nervous system, too, if the authors of [1] did the staining with their antibodies. If Cry4 and/or IscA1 were part of a magnetic sensory system, we would expect at least one of the proteins to be located only in a subset of cells forming part of a specific sensory pathway [8]. According to our experience, when an antibody stains more or less all cells in the retina, it either detects a very common housekeeping gene, which does not play a highly specific sensory role in a specific sensory system, or there is a problem with antibody specificity.