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.
authors: Danish Research Institute of Translational Neuroscience - DANDRITE, Nordic EMBL Partnership for Molecular Medicine, Aarhus University, DK-8000 Aarhus, Denmark.|Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.|Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, DK-8000 Aarhus, Denmark.
authors: Florian
authors: F
authors: Hilbers
authors: MEMPHYS: Centre for Biomembrane Physics, University of Southern Denmark, DK-8000 Aarhus, Denmark.
authors: Wojciech
authors: W
authors: Kopec
authors: Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, DK-8000 Aarhus, Denmark.|Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.
authors: Toke Jost
authors: TJ
authors: Isaksen
authors: Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, DK-8000 Aarhus, Denmark.|Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.
authors: Thomas Hellesøe
authors: TH
authors: Holm
authors: Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, DK-8000 Aarhus, Denmark.|Department of Biomedicine, Aarhus University, DK-8000 Aarhus, Denmark.|Aarhus Institute of Advanced Studies (AIAS), Aarhus University, DK-8000 Aarhus, Denmark.
authors: Karin
authors: K
authors: Lykke-Hartmann
authors: Danish Research Institute of Translational Neuroscience - DANDRITE, Nordic EMBL Partnership for Molecular Medicine, Aarhus University, DK-8000 Aarhus, Denmark.|Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.|Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, DK-8000 Aarhus, Denmark.
authors: Poul
authors: P
authors: Nissen
authors: MEMPHYS: Centre for Biomembrane Physics, University of Southern Denmark, DK-8000 Aarhus, Denmark.
authors: Himanshu
authors: H
authors: Khandelia
authors: Danish Research Institute of Translational Neuroscience - DANDRITE, Nordic EMBL Partnership for Molecular Medicine, Aarhus University, DK-8000 Aarhus, Denmark.|Department of Molecular Biology and Genetics, Aarhus University, DK-8000 Aarhus, Denmark.|Centre for Membrane Pumps in Cells and Disease - PUMPKIN, Danish National Research Foundation, DK-8000 Aarhus, Denmark.
authors: Hanne
authors: H
authors: Poulsen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002531:Cerebellum / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007477:Ions / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D056004:Molecular Dynamics Simulation; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000254:growth & development / Q000378:metabolism
chemical_list: D007477:Ions; D008051:Lipid Bilayers; D021122:Protein Subunits; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase