Tomita Atsuhiro, Zhang Mingfeng, Jin Fei, Zhuang Wenhui, Takeda Hironori, Maruyama Tatsuro, Osawa Masanori, Hashimoto Ken-Ichi, Kawasaki Hisashi, Ito Koichi, Dohmae Naoshi, Ishitani Ryuichiro, Shimada Ichio, Yan Zhiqiang, Hattori Motoyuki, Nureki Osamu
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan.
State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center of Genetics and Development, Institute of Brain Science, Department of Physiology and Biophysics, School of Life Sciences, Fudan University, 2005 Songhu Road, Yangpu District, Shanghai, 200438, China.
Nat Commun. 2017 Jul 27;8(1):148. doi: 10.1038/s41467-017-00082-w.
Magnesium is an essential ion for numerous physiological processes. MgtE is a Mg selective channel involved in the maintenance of intracellular Mg homeostasis, whose gating is regulated by intracellular Mg levels. Here, we report that ATP binds to MgtE, regulating its Mg-dependent gating. Crystal structures of MgtE-ATP complex show that ATP binds to the intracellular CBS domain of MgtE. Functional studies support that ATP binding to MgtE enhances the intracellular domain affinity for Mg within physiological concentrations of this divalent cation, enabling MgtE to function as an in vivo Mg sensor. ATP dissociation from MgtE upregulates Mg influx at both high and low intracellular Mg concentrations. Using site-directed mutagenesis and structure based-electrophysiological and biochemical analyses, we identify key residues and main structural changes involved in the process. This work provides the molecular basis of ATP-dependent modulation of MgtE in Mg homeostasis.MgtE is an Mg transporter involved in Mg homeostasis. Here, the authors report that ATP regulates the Mg-dependent gating of MgtE and use X-ray crystallography combined with functional studies to propose the molecular mechanisms involved in this process.
镁是众多生理过程所必需的离子。MgtE是一种参与维持细胞内镁稳态的镁选择性通道，其门控受细胞内镁水平的调节。在此，我们报告ATP与MgtE结合，调节其镁依赖性门控。MgtE - ATP复合物的晶体结构表明，ATP与MgtE的细胞内CBS结构域结合。功能研究支持，在这种二价阳离子的生理浓度范围内，ATP与MgtE结合增强了细胞内结构域对镁的亲和力，使MgtE能够作为体内镁传感器发挥作用。ATP从MgtE解离在细胞内镁浓度高和低时均会上调镁内流。通过定点诱变以及基于结构的电生理和生化分析，我们确定了该过程中涉及的关键残基和主要结构变化。这项工作为镁稳态中MgtE的ATP依赖性调节提供了分子基础。MgtE是一种参与镁稳态的镁转运体。在此，作者报告ATP调节MgtE的镁依赖性门控，并结合功能研究利用X射线晶体学提出了该过程涉及的分子机制。
