Mg2+-dependent interactions of ATP with the cystathionine- β-synthase (CBS) domains of a magnesium transporter

Yusuke Hirata, Yosuke Funato, Yu Takano, Hiroaki Miki

研究成果: Article査読

53 被引用数 (Scopus)

抄録

Ancient conserved domain protein/cyclin M (CNNM) family proteins are evolutionarily conserved Mg2+ transporters. However, their biochemical mechanism of action remains unknown. Here, we show the functional importance of the commonly conserved cystathionine- β-synthase (CBS) domains and reveal their unique binding ability to ATP. Deletion mutants of CNNM2 and CNNM4, lacking the CBS domains, are unable to promote Mg2+ efflux. Furthermore, the substitution of one amino acid residue in the CBS domains of CNNM2, which is associated with human hereditary hypomagnesemia, abrogates Mg2+ efflux. Binding analyses reveal that the CBS domains of CNNM2 bind directly to ATP and not AMP in a manner dependent on the presence of Mg2+, which is inhibited in a similar pattern by the disease-associated amino acid substitution. The requirement of Mg2+ for these interactions is a unique feature among CBS domains, which can be explained by the presence of highly electronegative surface potentials around the ATP binding site on CNNM2. These results demonstrate that the CBS domains play essential roles in Mg2+ efflux, probably through interactions with ATP. Interactions with ATP, which mostly forms complexes with Mg 2+ in cells, may account for the rapid Mg2+ transport by CNNM family proteins.

本文言語English
ページ(範囲)14731-14739
ページ数9
ジャーナルJournal of Biological Chemistry
289
21
DOI
出版ステータスPublished - 2014
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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