Systematic comparison of molecular conformations of H+,K+-ATPase reveals an important contribution of the A-M2 linker for the luminal gating.
Bottom Line: The molecular conformation of the (SCH)E2·MgF state thus represents a mixed overall structure in which its cytoplasmic and luminal half appear to be independently modulated by a phosphate analog and an antagonist bound to the respective parts of the enzyme.Comparison of the molecular conformations revealed that the linker region connecting the A domain and the transmembrane helix 2 (A-M2 linker) mediates the regulation of luminal gating.The mechanistic rationale underlying luminal gating observed in H(+),K(+)-ATPase is consistent with that observed in sarcoplasmic reticulum Ca(2+)-ATPase and other P-type ATPases and is most likely conserved for the P-type ATPase family in general.
Affiliation: From the Cellular and Structural Physiology Institute and Graduate School of Pharmaceutical Science, Nagoya University, Nagoya 464-8601, Japan email@example.com.Show MeSH
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Mentions: Gastric H+,K+-ATPase is an ATP-driven proton pump responsible for the gastric acid secretion (1, 2). This enzyme catalyzes the energetically uphill, electro-neutral exchange of H+/K+ coupled with ATP hydrolysis, which generates a million-fold H+-gradient across the parietal cell membrane (i.e. pH 1 in the stomach versus pH 7 in the cytosol; see Refs. 3 and 4). Like other P-type ATPases, the enzyme undergoes cyclical conformational changes between two principal reaction states (E1, E2) and their auto-phosphorylated forms (E1P, E2P) during its transport cycle (see Fig. 1 and Refs. 5–7).
Affiliation: From the Cellular and Structural Physiology Institute and Graduate School of Pharmaceutical Science, Nagoya University, Nagoya 464-8601, Japan firstname.lastname@example.org.