Crystal structure of the plasma membrane proton pump

  title={Crystal structure of the plasma membrane proton pump},
  author={Bj{\o}rn Panyella Pedersen and Morten Jeppe Buch-Pedersen and Jens Preben Morth and Michael Palmgren and Poul Nissen},
A prerequisite for life is the ability to maintain electrochemical imbalances across biomembranes. In all eukaryotes the plasma membrane potential and secondary transport systems are energized by the activity of P-type ATPase membrane proteins: H+-ATPase (the proton pump) in plants and fungi, and Na+,K+-ATPase (the sodium–potassium pump) in animals. The name P-type derives from the fact that these proteins exploit a phosphorylated reaction cycle intermediate of ATP hydrolysis. The plasma… 
The plant plasma membrane proton pump ATPase: a highly regulated P-type ATPase with multiple physiological roles
  • G. Duby, M. 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.
Protons and how they are transported by proton pumps
Taking the biochemical and structural data together, the basic molecular components that allow the plasma membrane proton H+-ATPase to carry out proton transport against large membrane potentials are described.
The plasma membrane H+‐ATPase, a simple polypeptide with a long history
The work that led to these insights in plasma membrane H+‐ATPases of fungi and plants has a long history, which is briefly summarized in this review.
In Silico Identification of Putative Proton Binding Sites of a Plasma Membrane H + -ATPase Isoform of Arabidopsis Thaliana , AHA1
Homology modeling along with transmembrane topology predictions has been used to build the atomic model of AHA1, another plasma membrane H + -ATPase isoform of Arabidopsis thaliana expressing in both root and shoot, suggesting that the enzyme isoform evolution may not be linked to its tissue-specific expression.
Mechanism and significance of P4 ATPase-catalyzed lipid transport: lessons from a Na+/K+-pump.
Metal Fluoride Inhibition of a P-type H+ Pump
It is indicated that the phosphate bond of the phosphoenzyme intermediate of H+-ATPases is labile in the basal state, which may provide an explanation for the low H+/ATP coupling ratio of these pumps inThe basal state.
The sarcoplasmic Ca2+-ATPase: design of a perfect chemi-osmotic pump
The detailed construction of the ATPase is described in terms of one membraneous and three cytosolic domains held together by a central core that mediates coupling between Ca2+-transport and ATP hydrolysis and the role of the lipid phase and the regulatory and thermodynamic aspects of the transport mechanism are reviewed.
A structural overview of the plasma membrane Na+,K+-ATPase and H+-ATPase ion pumps
Structural information provides insight into the function of these two distinct but related P-type pumps, which maintain a proton gradient in plants and fungi and a Na+ and K+ gradient in animal cells.
Direct observation of proton pumping by a eukaryotic P-type ATPase
Monitoring at the single-molecule level the activity of the prototypic proton-pumping P-type ATPase Arabidopsis thaliana isoform 2 revealed that pumping is stochastically interrupted by long-lived inactive or leaky states, and it is anticipated that similar functional dynamics underlie the operation and regulation of many other active transporters.
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.


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.
Abolishment of Proton Pumping and Accumulation in the E 1P Conformational State of a Plant Plasma Membrane H+-ATPase by Substitution of a Conserved Aspartyl Residue in Transmembrane Segment 6*
It is concluded that the mutant enzyme is locked in theE 1 conformation and is unable to proceed through the E 1P-E 2P transition, and there is evidence that Asp684 in the plasma membrane H-ATPase is required for any coupling between ATP hydrolysis, enzyme conformational changes, and H-transport.
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.
The Na,K-ATPase
Attention will be given to the biochemical characterization of the reaction mechanism underlying the coupling between hydrolysis of the substate ATP and transport of Na+ and K+.
Structure of the ATP Binding Domain from the Archaeoglobus fulgidus Cu+-ATPase*
The structure of the CopA ATP binding domain (ATPBD) provides a basis for understanding the likely structural and functional effects of various mutations that lead to Wilson and Menkes diseases.
Yeast plasma membrane ATPase is essential for growth and has homology with (Na+ + K+), K+- and Ca2+-ATPases
The strong homology between the ammo-acid sequence encoded by PMA1 and those of (Na+ + K+), Na+-, K+- and Ca2+-ATPases is consistent with the notion that the family of cation pumps which form a phosphorylated intermediate evolved from a common ancestral ATPase.
Structure-Function Relationships in Membrane Segment 5 of the Yeast Pma1 H+-ATPase*
A critical role is indicated for this membrane segment in protein folding and in the conformational changes that accompany the reaction cycle for yeast H+-ATPase by alanine-scanning mutagenesis.
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.
Structural changes in the calcium pump accompanying the dissociation of calcium
The structure of the enzyme stabilized by thapsigargin, a potent inhibitor, shows large conformation differences from that in E1Ca2+.
Modulatory and catalytic modes of ATP binding by the calcium pump
A mechanism of Ca2+ activation of phosphorylation leading directly from the compact E2‐ATP form to the Ca2E1‐ATp state is proposed and a role of Glu439 in ATP modulation of other steps of the functional cycle is suggested.