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: Transport cycle of gastric H+,K+-ATPase and reaction sub-steps induced by XFs.Upper panel, ion transport and ATP hydrolysis are coupled to the cyclic conformational conversion of the enzyme (abbreviated as E) between its main states, E1 and E2, and their respective auto-phosphorylated forms, E1P and E2P. ATP hydrolysis generates the phosphoenzyme intermediate (E1P, E2P) by transfer of the γ-phosphate to the invariant Asp-386 residue in the presence of Mg2+ (omitted in the figure for simplicity). Lower panel, E2P and its dephosphorylation steps mimicked by XFs are shown (see “Cytoplasmic Domains” for details). The atomic models represent the coordination chemistry of XFs (sticks for an aspartate residue and spheres for BeF3 (left), AlF4 and a water (middle), and MgF4 (right), respectively). Schematics of the molecular conformations presented in this study are shown (see Fig. 9 for details).
Affiliation: From the Cellular and Structural Physiology Institute and Graduate School of Pharmaceutical Science, Nagoya University, Nagoya 464-8601, Japan firstname.lastname@example.org.