A single K+-binding site in the crystal structure of the gastric proton pump

Kenta Yamamoto, Vikas Dubey, Katsumasa Irie, Hanayo Nakanishi, Himanshu Khandelia, Yoshinori Fujiyoshi, Kazuhiro Abe

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The gastric proton pump (H+,K+-ATPase), a P-type ATPase responsible for gastric acidification, mediates electro-neutral exchange of H+ and K+ coupled with ATP hydrolysis, but with an as yet undetermined transport stoichiometry. Here we show crystal structures at a resolution of 2.5 A° of the pump in the E2-P transition state, in which the counter-transporting cation is occluded. We found a single K+ bound to the cation-binding site of the H+,K+-ATPase, indicating an exchange of 1H+/1K+ per hydrolysis of one ATP molecule. This fulfills the energy requirement for the generation of a six pH unit gradient across the membrane. The structural basis of K+ recognition is resolved and supported by molecular dynamics simulations, establishing how the H+,K+-ATPase overcomes the energetic challenge to generate an H+ gradient of more than a million-fold—one of the highest cation gradients known in mammalian tissue—across the membrane.

Original languageEnglish
Article numbere47701
Number of pages22
Publication statusPublished - 22. Aug 2019


  • biochemistry
  • chemical biology
  • E. coli
  • gastric
  • human
  • membrane transport
  • molecular biophysics
  • P-type ATPase
  • proton pump
  • structural biology


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