ATP-dependent modulation of MgtE in Mg2+ homeostasis

被引：56

作者：

Tomita, Atsuhiro ^{[1
]}

Zhang, Mingfeng ^{[2
]}

Jin, Fei ^{[3
]}

Zhuang, Wenhui ^{[2
]}

Takeda, Hironori ^{[4
]}

Maruyama, Tatsuro ^{[5
]}

Osawa, Masanori ^{[5
]}

Hashimoto, Ken-ichi ^{[6
]}

Kawasaki, Hisashi ^{[6
]}

Ito, Koichi ^{[7
]}

Dohmae, Naoshi ^{[8
]}

Ishitani, Ryuichiro ^{[1
]}

Shimada, Ichio ^{[5
]}

Yan, Zhiqiang ^{[2
,9
]}

Hattori, Motoyuki ^{[3
]}

Nureki, Osamu ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Sci, Dept Biol Sci, Bunkyo Ku, 2-11-16 Yayoi, Tokyo 1130032, Japan

[2] Fudan Univ, Collaborat Innovat Ctr Genet & Dev, State Key Lab Med Neurobiol, Inst Brain Sci,Dept Physiol & Biophys,Sch Life Sc, 2005 Songhu Rd, Shanghai 200438, Peoples R China

[3] Fudan Univ, Collaborat Innovat Ctr Genet & Dev, State Key Lab Genet Engn, Dept Physiol & Biophys,Sch Life Sci, 2005 Songhu Rd, Shanghai 200438, Peoples R China

[4] Kyoto Sangyo Univ, Fac Life Sci, Kita Ku, Kamigamo Motoyama, Kyoto 6038555, Japan

[5] Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Hongo, Tokyo 1130033, Japan

[6] Tokyo Denki Univ, Dept Green & Sustainable Chem, Adachi Ku, 5 Asahi Cho, Senju, Tokyo 1208551, Japan

[7] Univ Tokyo, Grad Sch Frontier Sci, Dept Computat Biol & Med Sci, 5-1-5 Kashiwanoha, Kashiwa, Chiba 2778562, Japan

[8] RIKEN Ctr Sustainable Resource Sci, Biomol Characterizat Unit, 2-1 Hirosawa, Wako, Saitama 3510198, Japan

[9] Southwest Med Univ, Sch Basic Med Sci, Dept Human Anat, Luzhou 646000, Sichuan, Peoples R China

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

中国国家自然科学基金;

关键词：

CRYSTAL-STRUCTURE; STRUCTURAL BASIS; CBS DOMAINS; MAGNESIUM TRANSPORTER; CYTOPLASMIC DOMAIN; MECHANISM; CHANNELS; SLC41A1; PHOSPHATE; VIRULENCE;

D O I：

10.1038/s41467-017-00082-w

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Magnesium is an essential ion for numerous physiological processes. MgtE is a Mg2+ selective channel involved in the maintenance of intracellular Mg2+ homeostasis, whose gating is regulated by intracellular Mg2+ levels. Here, we report that ATP binds to MgtE, regulating its Mg2+-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 Mg2+ within physiological concentrations of this divalent cation, enabling MgtE to function as an in vivo Mg2+ sensor. ATP dissociation from MgtE upregulates Mg2+ influx at both high and low intracellular Mg2+ 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 Mg2+ homeostasis.

引用

页数：11

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