title: Mg2+-sensing mechanism of Mg2+ transporter MgtE probed by molecular dynamics study.
abstract: Proper regulation of the intracellular ion concentration is essential to maintain life and is achieved by ion transporters that transport their substrates across the membrane in a strictly regulated manner. MgtE is a Mg(2+) transporter that may function in the homeostasis of the intracellular Mg(2+) concentration. A recent crystallographic study revealed that its cytosolic domain undergoes a Mg(2+)-dependent structural change, which is proposed to gate the ion-conducting pore passing through the transmembrane domain. However, the dynamics of Mg(2+) sensing, i.e., how MgtE responds to the change in the intracellular Mg(2+) concentration, remained elusive. Here we performed molecular dynamics simulations of the MgtE cytosolic domain. The simulations successfully reproduced the structural changes of the cytosolic domain upon binding or releasing Mg(2+), as well as the ion selectivity. These results suggested the roles of the N and CBS domains in the cytosolic domain and their respective Mg(2+) binding sites. Combined with the current crystal structures, we propose an atomically detailed model of Mg(2+) sensing by MgtE.
authors.affiliation: Division of Structure Biology, Department of Basic Medical Science, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. ishitani@ims.u-tokyo.ac.jp
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Ishitani
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sugita
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Noritaka
authors.initials: N
authors.lastname: Furuya
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Hattori
authors.forename: Osamu
authors.initials: O
authors.lastname: Nureki
mesh_terms: D017920:Antiporters / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D003600:Cytosol / Q000378:metabolism; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D017920:Antiporters; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C092192:MgtE protein, bacteria; D008274:Magnesium