論文

2022年9月9日

Structure and function of H+/K+ pump mutants reveal Na+/K+ pump mechanisms

Nature Communications
  • Victoria C. Young
  • ,
  • Hanayo Nakanishi
  • ,
  • Dylan J. Meyer
  • ,
  • Tomohiro Nishizawa
  • ,
  • Atsunori Oshima
  • ,
  • Pablo Artigas
  • ,
  • Kazuhiro Abe

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記述言語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41467-022-32793-0
出版者・発行元
Springer Science and Business Media LLC

Abstract

Ion-transport mechanisms evolve by changing ion-selectivity, such as switching from Na+ to H+ selectivity in secondary-active transporters or P-type-ATPases. Here we study primary-active transport via P-type ATPases using functional and structural analyses to demonstrate that four simultaneous residue substitutions transform the non-gastric H+/K+ pump, a strict H+-dependent electroneutral P-type ATPase, into a bona fide Na+-dependent electrogenic Na+/K+ pump. Conversion of a H+-dependent primary-active transporter into a Na+-dependent one provides a prototype for similar studies of ion-transport proteins. Moreover, we solve the structures of the wild-type non-gastric H+/K+ pump, a suitable drug target to treat cystic fibrosis, and of its Na+/K+ pump-mimicking mutant in two major conformations, providing insight on how Na+ binding drives a concerted mechanism leading to Na+/K+ pump phosphorylation.

リンク情報
DOI
https://doi.org/10.1038/s41467-022-32793-0
URL
https://www.nature.com/articles/s41467-022-32793-0.pdf
URL
https://www.nature.com/articles/s41467-022-32793-0
ID情報
  • DOI : 10.1038/s41467-022-32793-0
  • eISSN : 2041-1723

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