Key Points
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P-type ATPases use the energy from ATP hydrolysis to pump ions across the cell membrane against a concentration gradient.
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They form a large family of ubiquitous membrane proteins, and carry out many essential processes, such as generating the membrane potential or removing toxic ions from cells.
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P-type ATPases undergo large conformational changes in the ion-pumping cycle. Recent X-ray and electron-microscopy structures of P-type ATPases in different conformations have provided the first detailed insights into the mechanism of ATP-driven ion translocation.
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The common structural elements of all P-type ATPases are four protein domains, each with highly conserved features, which indicates that they all share the same basic mechanism.
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The 10 membrane-spanning α-helices of the membrane domain form the ion-translocation site and provide a mechanical link to the three cytoplasmic domains that carry out ATP hydrolysis
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The activity of most P-type ATPases is tightly controlled by extra regulatory domains or protein subunits. The regulatory mechanisms are poorly understood.
Abstract
P-type ATPases are ion pumps that carry out many fundamental processes in biology and medicine, ranging from the generation of membrane potential to muscle contraction and the removal of toxic ions from cells. Making use of the energy stored in ATP, they transport specific ions across the cell membrane against a concentration gradient. 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.
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Acknowledgements
I thank Gitte Mohsin and Paolo Lastrico for preparing the figures, and Mickey Palmgren for many helpful hints.
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Glossary
- MEMBRANE POTENTIAL
-
The charge difference (measured in mV) between the two surfaces of a biological membrane that arises from the different concentrations of ions such as H+, Na+ or K+ on either side. The Na+/K+-ATPase creates a membrane potential by using the energy stored in ATP to maintain a low concentration of Na+ and a high concentration of K+ in the cell, against a higher concentration of Na+ and a lower concentration of K+ on the outside.
- FXYD PROTEIN FAMILY
-
A small family of short, single-span membrane proteins that contain the FXYD sequence motif (in which X can be any amino acid). Most known FXYD proteins regulate the activity of Na+/K+-ATPases in particular tissues. For example, the FXYD protein phospholemman regulates Na+/K+-ATPases in heart and skeletal muscle, and the γ-subunit, another FXYD protein, regulates renal Na+/K+-ATPase.
- ROSSMANN FOLD
-
A common structural motif that is found in the nucleotide-binding domains of many proteins. The typical Rossmann fold (named after the eminent protein crystallographer Michael Rossmann) consists of two structurally similar halves, each with three β-strands and two α-helices. The two halves are connected by a linking helix, and form a compact, globular α/β domain with a central, six-stranded parallel β-sheet.
- 14-3-3 PROTEINS
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A large class of proteins that are involved in cell division, apoptosis, signal transduction, transmitter release, receptor function, gene expression and enzyme activation in eukaryotes. They function by binding to a wide range of different, specific target proteins, usually in response to phosphorylation of these targets.
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Kühlbrandt, W. Biology, structure and mechanism of P-type ATPases. Nat Rev Mol Cell Biol 5, 282–295 (2004). https://doi.org/10.1038/nrm1354
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DOI: https://doi.org/10.1038/nrm1354
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