Novel Mg^(2+)binding sites in the cytoplasmic domain of the MgtE Mg^(2+)channels revealed by X-ray crystal structures  

作　　者：Mengqi Wang Yimeng Zhao Yoshiki Hayashi Koichi Ito Motoyuki Hattori 

机构地区：[1]State Key Laboratory of Genetic Engineering,Collaborative Innovation Center of Genetics and Development,Shanghai Key Laboratory of Bioactive Small Molecules,Department of Physiology and Neurobiology,School of Life Sciences,Fudan University,Shanghai 200438,China [2]Human Phenome Institute,Fudan University,Shanghai 201203,China [3]Department of Computational Biology and Medical Sciences,Graduate School of Frontier Sciences,The University of Tokyo,Chiba 277-8562,Japan

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第4期683-690,共8页生物化学与生物物理学报（英文版）

基　　金：the grants from the Ministry of Science and Technology of China(National Key R&D Program of China:No.2016YFA0502800 to M.H.);the National Natural Science Foundation of China(No.32071234 to M.H.);the Innovative Research Team of High-Level Local Universities in Shanghai and a Key Laboratory Program of the Education Commission of Shanghai Municipality(No.ZDSYS14005 to M.H.);the Open Research Fund of the State Key Laboratory of Genetic Engineering,Fudan University(No.SKLGE-2105 to M.H.);the China Postdoctoral Science Foundation(No.2021M690690 to Y.Z.)。

摘　　要：MgtE is a Mg^(2+)-selective channel regulated by the intracellular Mg^(2+)concentration.MgtE family proteins are highly conserved in all domains of life and contribute to cellular Mg^(2+)homeostasis.In humans,mutations in the SLC41 proteins,the eukaryotic counterparts of the bacterial MgtE,are known to be associated with various diseases.The first MgtE structure from a thermophilic bacterium,Thermus thermophilus,revealed that MgtE forms a homodimer consisting of transmembrane and cytoplasmic domains with a plug helix connecting the two and that the cytoplasmic domain possesses multiple Mg^(2+)binding sites.Structural and electrophysiological analyses revealed that the dissociation of Mg^(2+)ions from the cytoplasmic domain induces structural changes in the cytoplasmic domain,leading to channel opening.Thus,previous works showed the importance of MgtE cytoplasmic Mg^(2+)binding sites.Nevertheless,due to the limited structural information on MgtE from different species,the conservation and diversity of the cytoplasmic Mg^(2+)binding site in MgtE family proteins remain unclear.Here,we report crystal structures of the Mg^(2+)-bound MgtE cytoplasmic domains from two different bacterial species,Chryseobacterium hispalense and Clostridiales bacterium,and identify multiple Mg^(2+)binding sites,including ones that were not observed in the previous MgtE structure.These structures reveal the conservation and diversity of the cytoplasmic Mg^(2+)binding site in the MgtE family proteins.

关 键 词：ion channels MAGNESIUM metal homeostasis REGULATION crystal structure 

分 类 号：TG146.22[一般工业技术—材料科学与工程]