title: Structural basis for ion selectivity revealed by high-resolution crystal structure of Mg2+ channel MgtE.
abstract: Magnesium is the most abundant divalent cation in living cells and is crucial to several biological processes. MgtE is a Mg(2+) channel distributed in all domains of life that contributes to the maintenance of cellular Mg(2+) homeostasis. Here we report the high-resolution crystal structures of the transmembrane domain of MgtE, bound to Mg(2+), Mn(2+) and Ca(2+). The high-resolution Mg(2+)-bound crystal structure clearly visualized the hydrated Mg(2+) ion within its selectivity filter. Based on those structures and biochemical analyses, we propose a cation selectivity mechanism for MgtE in which the geometry of the hydration shell of the fully hydrated Mg(2+) ion is recognized by the side-chain carboxylate groups in the selectivity filter. This is in contrast to the K(+)-selective filter of KcsA, which recognizes a dehydrated K(+) ion. Our results further revealed a cation-binding site on the periplasmic side, which regulate channel opening and prevents conduction of near-cognate cations.
authors.affiliation: 1] Department of Biological Sciences, Graduate School of Science, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan [2] Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Takeda
authors.affiliation: 1] Department of Biological Sciences, Graduate School of Science, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan [2] Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan [3] Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan [4] School of Life Sciences, Fudan University, 220 Handan Road, Yangpu District, Shanghai 200433, China.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Hattori
authors.affiliation: 1] Department of Biological Sciences, Graduate School of Science, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan [2] Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nishizawa
authors.affiliation: SR Life Science Instrumentation Unit, RIKEN SPring-8 Center, 1-1-1 Kouto, Sayo-cho, Sayo-gun, Hyogo 679-5148, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Membrane Structural and Functional Biology Group, School of Medicine, and School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Syed T A
authors.initials: ST
authors.lastname: Shah
authors.affiliation: Membrane Structural and Functional Biology Group, School of Medicine, and School of Biochemistry and Immunology, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Martin
authors.initials: M
authors.lastname: Caffrey
authors.affiliation: Department of Bioengineering Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Andrés D
authors.initials: AD
authors.lastname: Maturana
authors.affiliation: 1] Department of Biological Sciences, Graduate School of Science, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan [2] Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Ishitani
authors.affiliation: 1] Department of Biological Sciences, Graduate School of Science, University of Tokyo, 2-11-16 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan [2] Global Research Cluster, RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nureki
mesh_terms: D017920:Antiporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli; D008274:Magnesium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017434:Protein Structure, Tertiary; D016963:Thermus thermophilus / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D017920:Antiporters; D001426:Bacterial Proteins; C092192:MgtE protein, bacteria; D008274:Magnesium