A hidden property of the iron–sulfur protein in the mononuclear iron‐bound state: species‐dependent structural ordering induced by magnetic fields

The iron-sulfur (Fe-S) cluster assembly homolog 1 (ISCA1) is a ubiquitous protein conserved in various organisms. Previous work has shown that a pigeon ISCA1 (clISCA1) forms columnar oligomers in the 2Fe-2S cluster-bound state, the length of which has been known to change in response to magnetic fields. However, whether this unique property is conserved in ISCA1 proteins of other species, particularly humans (hsISCA1), is unclear. Moreover, a recent study revealed that clISCA1 binds to not only Fe-S clusters but also mononuclear iron atoms, which may impart some magnetic properties to clISCA1. In this study, the electron spin resonance revealed that hsISCA1 also binds to mononuclear iron atoms. Moreover, the magnetic responses of Fe-S cluster-unbound ISCA1s (Fe-ISCA1s), which bind only mononuclear iron atoms, were inspected by small-angle X-ray scattering analyses for pigeon (Fe-clISCA1) and human (Fe-hsISCA1). The results indicated that Fe-hsISCA1 formed columnar oligomers under geomagnetic conditions, whereas Fe-clISCA1 formed dumbbell-like oligomers. When a magnetic field (180 mT) was applied, the Fe-hsISCA1 oligomer was shortened within 1 min and gradually elongated again after 10 min. This result indicates that mononuclear iron atoms contribute to the magnetically induced structural ordering of ISCA1, whereas the contribution of the Fe-S clusters to the columnarization of ISCA1 varies among species. Although the physiological role of the magnetic properties of ISCA1 is not yet elucidated, this study demonstrated that the magnetic field responsiveness of ISCA1 is conserved in humans. The magnetic field responsiveness may be a hidden fundamental property of ISCA1 that is maintained even if the Fe-S cluster is released.