6JXI

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

(2019) Elife 8

• PubMed: 31436534 Search on PubMedSearch on PubMed Central
• DOI: https://doi.org/10.7554/eLife.47701
• Primary Citation of Related Structures:  
  6JXH, 6JXI, 6JXJ, 6JXK


• PubMed 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.

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Organizational Affiliation: 

Cellular and Structural Physiology Institute, Nagoya University, Nagoya, Japan.