Iron-sulfur clusters are essential cofactors for proteins involved in various biological processes, such as electron transport, biosynthetic reactions, DNA repair, and gene expression regulation. Iron-sulfur cluster assembly protein IscA1 (or MagR) is found within the mitochondria of most eukaryotes. Magnetoreceptor (MagR) is a highly conserved A-type iron and iron-sulfur cluster-binding protein, characterized by two distinct types of iron-sulfur clusters, [2Fe-2S] and [3Fe-4S], each conferring unique magnetic properties. MagR forms a rod-like polymer structure in complex with photoreceptive cryptochrome (Cry) and serves as a putative magnetoreceptor for retrieving geomagnetic information in animal navigation. Although the N-terminal sequences of MagR vary among species, their specific function remains unknown. In the present study, we found that the N-terminal sequences of pigeon MagR, previously thought to serve as a mitochondrial targeting signal (MTS), were not cleaved following mitochondrial entry but instead modulated the efficiency with which iron-sulfur clusters and irons are bound. Moreover, the N-terminal region of MagR was required for the formation of a stable MagR/Cry complex. Thus, the N-terminal sequences in pigeon MagR fulfil more important functional roles than just mitochondrial targeting. These results further extend our understanding of the function of MagR and provide new insights into the origin of magnetoreception from an evolutionary perspective.
铁硫簇结合蛋白参与了众多生理过程，如电子传递、生物合成反应、DNA修复和基因表达调控等。磁受体 MagR，曾命名为铁硫簇组装蛋白IscA1，存在于很多真核生物的线粒体中。MagR是一种高度保守的A型铁和铁硫簇结合蛋白，能同时结合[2Fe-2S]和[3Fe-4S]两种铁硫簇，随着结合的铁硫簇的不同具有不同的磁学特征。MagR作为磁受体与感光的隐花色素蛋白（Cryptochrome，Cry）形成棍状复合物，在动物磁感应与生物导航中发挥作用。与细菌的同源蛋白 IscA 相比，真核生物的MagR在N端存在一段长度不等的序列，且这段序列在不同物种中存在较大差异，然而其具体功能尚不清楚。该研究以原鸽的MagR为例，验证了MagR的 N 端 25 个氨基酸序列（N25）具有线粒体定位功能。有意思的是，该序列在MagR进入线粒体后不仅没有被切除，还显著影响了MagR蛋白中铁硫簇和铁的结合效率。此外，该 N 端序列也在MagR与Cry蛋白的稳定复合物的形成中发挥着作用。因此，我们的研究表明原鸽MagR的N端序列不仅仅作为线粒体定位信号，同时还对 MagR 的生化功能起着重要的调节作用。该研究进一步拓展了我们对MagR功能的理解，同时从演化的角度为揭示生物磁感应起源提供了新的思路。.
Keywords: Iron-sulfur cluster; Magnetoreceptor (MagR); Mitochondrial targeting signal; N-terminal sequence.