重庆大学生物工程学院细胞生化与基因拓扑生物学实验室,重庆大学生物工程学院细胞生化与基因拓扑生物学实验室,重庆大学生物工程学院细胞生化与基因拓扑生物学实验室
国家自然科学基金资助项目(91429305,31270879)和重庆市研究生科研创新项目(CYB15024)
Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering, Chongqing University,Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering, Chongqing University,Laboratory of Cell Biochemistry and Topogenetic Regulation, College of Bioengineering, Chongqing University
This work was supported by grants from The National Natural Science Foundation of China (91429305, 31270879), Chongqing Graduate Research and Innovation Project (CYB15024)
铁硫簇蛋白是一类重要的线粒体功能蛋白,在细胞能量代谢、电子传递、底物结合与激活、铁/硫存储、酶促反应、基因表达调控等诸多过程中均发挥了关键作用.铁硫簇蛋白质组装及转运过程一旦发生障碍,必将严重影响细胞内铁的稳态及铁硫蛋白的功能.分子质量约11 ku的铁硫簇蛋白IscA,是铁硫蛋白亚家族hesB高保守性成员之一,能结合铁离子及[2Fe-2S]簇,参与铁硫簇蛋白质合成,因此IscA在铁硫簇组装蛋白与级联反应系统中具有重要的作用.更值得关注的是,2015年谢灿和张生家两个研究组发现IscA1具有磁受体(MagR/MAR)作用,此外,谢灿课题组揭示MagR能与Cry形成磁感应复合物行使磁感应器(magnetic sensor,MagS)功能.尤为重要的是,体内实验表明通过外磁场刺激活化MagR能调控相关磁基因表达,影响神经活动及行为定位.鉴于MagR磁受体的独特功能,张生家等将磁受体的基因定位与远程磁刺激相结合,发明了一种非损伤性的神经调控方法,称之为磁遗传学.本文简要介绍MagR/IscA及其同源基因的始初发现与鉴定历程、进化保守性、独特的生理生物学功能,并凝练出磁遗传假说机制调控模型,以解释MagR/IscA的磁遗传学功能.
An important class of mitochondrial function protein is referred to as an iron-sulfur cluster protein (Isc) family, which plays a vital role in the cellular energy metabolism, electron transfer, substrate-binding and activation, iron-sulfur storage, enzymatic reaction and gene regulation. Dysregulation in either the Isc assembly or transport processes would give rise to a deteriorative effect on both the intracellular iron homeostasis and the functionality of Isc-relevant proteins. Particularly, IscA (molecular mass, ~11 ku) is identified as a highly conserved member of the iron-sulfur protein hesB subfamily that can directly bind to iron ions and iron-sulfur [2Fe-2S] cluster and hence participates in the biosynthesis of iron sulfur cluster proteins. Thereby, IscA is postulated to display a paramount function in the iron-sulfur cluster assembly and cascade reaction system. Curiously, it is worth mentioning that two seemingly similar but different discoveries on the topic of IscA1 published respectively by Dr. Xie and Dr. Zhang’s groups in 2015, no matter whether they have attracted extensive public attention, unraveled that IscA1 possesses a putative magneto-receptor capability and thus IscA1 has been renamed as MagR/MAR in their papers. In addition, Xie’s group found that IscA could act as a magnetic sensor by means of forming magnetosensor (MagS) complex with Cry. Of crucial importance to notice, the expression of certain magneto-responsive genes in vivo could be regulated by the external magnetic field-stimulated activation of MagR, which would subsequently affect neural activity and the magnetic oriented animal behaviors. Regarding to the unique magneto-sensing function of MagR, the concept for “magnetogenetics” is proposed by Dr. Zhang’s group in combination of the genetic targeting to MagR/MAR with relevant remote magnetic stimulation. In this mini-review, we give a brief introduction into the discovery of MagR/IscA and its homologues together with their high evolutionary conservation, as well as current proceedings of researches on its physiological functions. Furthermore, we proposed an intracellular biomagnetic signaling-responsive mechanism insofar as to provide an explicit explanation of how MagR/IscA1 exerts it intrinsic function in magnetogenetics.
汪红霞,向远彩,张义国.生物磁受体蛋白MagR/IscA研究进展[J].生物化学与生物物理进展,2016,43(12):1115-1128
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