Structure, Mechanism, and Regulation of the Neurospora Plasma Membrane H+-ATPase

  title={Structure, Mechanism, and Regulation of the Neurospora Plasma Membrane H+-ATPase},
  author={Werner K{\"u}hlbrandt and Johan P. Zeelen and Jens Dietrich},
  pages={1692 - 1696}
Proton pumps in the plasma membrane of plants and yeasts maintain the intracellular pH and membrane potential. To gain insight into the molecular mechanisms of proton pumping, we built an atomic homology model of the proton pump based on the 2.6 angstrom x-ray structure of the related Ca2+ pump from rabbit sarcoplasmic reticulum. The model, when fitted to an 8 angstrom map of theNeurospora proton pump determined by electron microscopy, reveals the likely path of the proton through the membrane… 
Mechanism of Proton Pumping by Plant Plasma Membrane H+‐ATPase
Site‐directed mutagenesis studies suggest that Asp684, situated in transmembrane segment M6, is involved in coordination of proton(s) in plant plasma membrane H+‐ATPase.
The plant plasma membrane proton pump ATPase: a highly regulated P-type ATPase with multiple physiological roles
  • G. DubyM. Boutry
  • Biology, Chemistry
    Pflügers Archiv - European Journal of Physiology
  • 2008
Crystallographic data and homology modeling suggest that the H+-ATPase has a broadly similar structure to the other P-type ATPases but has an extended C-terminal region, which is involved in enzyme regulation, and the recent identification of additional phosphorylated residues suggests further regulatory features.
The yeast and plant plasma membrane H+ pump ATPase: divergent regulation for the same function.
Structure and activation mechanism of the hexameric plasma membrane H+-ATPase
A high-resolution cryo-EM study of native Pma1 hexamers embedded in endogenous lipids reveals a detailed mechanism for ATP-hydrolysis-driven proton pumping across the plasma membrane, which will facilitate the development of antifungal drugs that target this essential protein.
Biology, structure and mechanism of P-type ATPases
Recent X-ray structures and homology models of P-type pumps now provide a basis for understanding the molecular mechanism of ATP-driven ion transport.
Structure and function of the calcium pump.
  • D. StokesN. Green
  • Chemistry
    Annual review of biophysics and biomolecular structure
  • 2003
Comparisons of various structures and correlating functional data can be compared to associate the chemical changes constituting the reaction cycle with structural changes in these domains, and identify the Ca2+-ATPase domains affected by these changes.
Conserved Asp684 in Transmembrane Segment M6 of the Plant Plasma Membrane P-type Proton Pump AHA2 Is a Molecular Determinant of Proton Translocation*
The finding that the carboxylate side chain of Asp684 contributes to the proton-binding site and appears to function as an absolutely essential proton acceptor along the propton transport pathway is discussed in the context of a possible proton pumping mechanism of P-type H+-ATPases.
Essential Glycine in the Proton Channel of Escherichia coli Transhydrogenase*
Gly252 mutants are distinguished by high levels of cyclic transhydrogenation activity in the absence of added NADP(H) and by complete loss of proton pumping activity, implying that Gly252 mutants exhibit a native-like domain II conformation while blocking proton translocation and coupled exchange of NADP (H) in domain III.
Effects of C-terminal Truncations on Trafficking of the Yeast Plasma Membrane H+-ATPase*
A series of truncations affirms the importance of the entire C-terminal domain to yeast H+-ATPase biogenesis and defines a sequence element of 20 amino acids in the carboxyl tail that is critical to ER escape and trafficking to the plasma membrane.


Three-dimensional map of the plasma membrane H+-ATPase in the open conformation
A three-dimensional map of the H+-ATPase is obtained by electron crystallography of two-dimensional crystals grown directly on electron microscope grids and reveals ten membrane-spanning α-helices in the membrane domain, and four major cytoplasmic domains in the open conformation of the enzyme without bound ligands.
Regulation of Yeast H+-ATPase by Protein Kinases Belonging to a Family Dedicated to Activation of Plasma Membrane Transporters
Two genes from Saccharomyces cerevisiae are characterized that encode protein kinases implicated in activation of the yeast plasma membrane H+-ATPase (Pma1) in response to glucose metabolism, and ptk2 mutants exhibited reduced uptake of lithium and methylammonium.
Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 Å resolution
Comparison with a low-resolution electron density map of the enzyme in the absence of calcium and with biochemical data suggests that large domain movements take place during active transport.
Domain movements of plasma membrane H+‐ATPase: 3D structures of two states by electron cryo‐microscopy
Structural comparisons indicate that there is a rearrangement of the cytoplasmic domain on Mg2+/ADP binding, which consists of a movement of mass towards the 6‐fold axis causing the structure to become more compact, accompanied by a modest conformational change in the transmembrane domain.
Structure of the calcium pump from sarcoplasmic reticulum at 8-Å resolution
A distinct cavity leads to the putative calcium-binding site, providing a plausible path for calcium release to the lumen of the sarcoplasmic reticulum.
The regulatory domain of fungal and plant plasma membrane H(+)-ATPase.
The activity of fungal and plant plasma membrane H(+)-ATPases seems to be regulated by modulation of the interaction of an inhibitory domain at the C-terminus with the active site, and genetic evidence for domain interaction is provided.
A structural model for the catalytic cycle of Ca(2+)-ATPase.
It is hypothesized that both the nucleotide-binding and beta-sheet domains are highly mobile and driven by Brownian motion to elicit phosphoenzyme formation and calcium transport, respectively, and the reaction cycle of Ca(2+)-ATPase would have elements of a Brownian ratchet.