Tuning of the Na,K-ATPase by the beta subunit.

Florian Hilbers; Wojciech Kopec; Toke Jost Isaksen; Thomas Hellesøe Holm; Karin Lykke-Hartmann; Poul Nissen; Himanshu Khandelia; Hanne Poulsen

doi:10.1038/srep20442

Tuning of the Na,K-ATPase by the beta subunit.

Florian Hilbers, Wojciech Kopec, Toke Jost Isaksen, Thomas Hellesøe Holm, Karin Lykke-Hartmann, Poul Nissen, Himanshu Khandelia, Hanne Poulsen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

The vital gradients of Na ⁺ and K ⁺ across the plasma membrane of animal cells are maintained by the Na,K-ATPase, an αβ enzyme complex, whose α subunit carries out the ion transport and ATP hydrolysis. The specific roles of the β subunit isoforms are less clear, though β2 is essential for motor physiology in mammals. Here, we show that compared to β1 and β3, β2 stabilizes the Na ⁺-occluded E1P state relative to the outward-open E2P state, and that the effect is mediated by its transmembrane domain. Molecular dynamics simulations further demonstrate that the tilt angle of the β transmembrane helix correlates with its functional effect, suggesting that the relative orientation of β modulates ion binding at the α subunit. β2 is primarily expressed in granule neurons and glomeruli in the cerebellum, and we propose that its unique functional characteristics are important to respond appropriately to the cerebellar Na ⁺ and K ⁺ gradients.

Original language	English
Article number	20442
Journal	Scientific Reports
Volume	6
Issue	20442
ISSN	2045-2322
DOIs	https://doi.org/10.1038/srep20442
Publication status	Published - 2016

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title = "Tuning of the Na,K-ATPase by the beta subunit.",

abstract = "The vital gradients of Na + and K + across the plasma membrane of animal cells are maintained by the Na,K-ATPase, an αβ enzyme complex, whose α subunit carries out the ion transport and ATP hydrolysis. The specific roles of the β subunit isoforms are less clear, though β2 is essential for motor physiology in mammals. Here, we show that compared to β1 and β3, β2 stabilizes the Na +-occluded E1P state relative to the outward-open E2P state, and that the effect is mediated by its transmembrane domain. Molecular dynamics simulations further demonstrate that the tilt angle of the β transmembrane helix correlates with its functional effect, suggesting that the relative orientation of β modulates ion binding at the α subunit. β2 is primarily expressed in granule neurons and glomeruli in the cerebellum, and we propose that its unique functional characteristics are important to respond appropriately to the cerebellar Na + and K + gradients. ",

author = "Florian Hilbers and Wojciech Kopec and Isaksen, {Toke Jost} and Holm, {Thomas Helles{\o}e} and Karin Lykke-Hartmann and Poul Nissen and Himanshu Khandelia and Hanne Poulsen",

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AU - Hilbers, Florian

AU - Kopec, Wojciech

AU - Isaksen, Toke Jost

AU - Holm, Thomas Hellesøe

AU - Lykke-Hartmann, Karin

AU - Nissen, Poul

AU - Khandelia, Himanshu

AU - Poulsen, Hanne

PY - 2016

Y1 - 2016

N2 - The vital gradients of Na + and K + across the plasma membrane of animal cells are maintained by the Na,K-ATPase, an αβ enzyme complex, whose α subunit carries out the ion transport and ATP hydrolysis. The specific roles of the β subunit isoforms are less clear, though β2 is essential for motor physiology in mammals. Here, we show that compared to β1 and β3, β2 stabilizes the Na +-occluded E1P state relative to the outward-open E2P state, and that the effect is mediated by its transmembrane domain. Molecular dynamics simulations further demonstrate that the tilt angle of the β transmembrane helix correlates with its functional effect, suggesting that the relative orientation of β modulates ion binding at the α subunit. β2 is primarily expressed in granule neurons and glomeruli in the cerebellum, and we propose that its unique functional characteristics are important to respond appropriately to the cerebellar Na + and K + gradients.

AB - The vital gradients of Na + and K + across the plasma membrane of animal cells are maintained by the Na,K-ATPase, an αβ enzyme complex, whose α subunit carries out the ion transport and ATP hydrolysis. The specific roles of the β subunit isoforms are less clear, though β2 is essential for motor physiology in mammals. Here, we show that compared to β1 and β3, β2 stabilizes the Na +-occluded E1P state relative to the outward-open E2P state, and that the effect is mediated by its transmembrane domain. Molecular dynamics simulations further demonstrate that the tilt angle of the β transmembrane helix correlates with its functional effect, suggesting that the relative orientation of β modulates ion binding at the α subunit. β2 is primarily expressed in granule neurons and glomeruli in the cerebellum, and we propose that its unique functional characteristics are important to respond appropriately to the cerebellar Na + and K + gradients.

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ER -

Tuning of the Na,K-ATPase by the beta subunit.

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