4.8 Article

Structural basis for ion selectivity revealed by high-resolution crystal structure of Mg2+ channel MgtE

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NATURE COMMUNICATIONS
卷 5, 期 -, 页码 -

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NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms6374

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  1. Platform for Drug Discovery
  2. Ministry of Education, Culture, Sports, Science and Technology (MEXT)
  3. JSPS KAKENHI [22117007, 24227004, 25291011, 26711003]
  4. FIRST programme
  5. PRESTO
  6. JST
  7. HPCI STRATEGIC PROGRAM Computational Life Science and Application in Drug Discovery
  8. MEXT
  9. Private University Strategic Research Foundation Support Program (MEXT)

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Magnesium is the most abundant divalent cation in living cells and is crucial to several biological processes. MgtE is a Mg2+ channel distributed in all domains of life that contributes to the maintenance of cellular Mg2+ homeostasis. Here we report the highresolution crystal structures of the transmembrane domain of MgtE, bound to Mg2+, Mn2+ and Ca2+. The high-resolution Mg2+ bound crystal structure clearly visualized the hydrated Mg2+ 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 Mg2+ 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.

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