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

ABSTRACT: 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 Å 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.

SUBMITTER: Yamamoto K

PROVIDER: S-EPMC6706254 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Yamamoto Kenta K Dubey Vikas V Irie Katsumasa K Nakanishi Hanayo H Khandelia Himanshu H Fujiyoshi Yoshinori Y Abe Kazuhiro K

eLife 20190822

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 Å 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<s ...[more]

PMID: 31436534

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