Hilbers Florian, Kopec Wojciech, Isaksen Toke Jost, Holm Thomas Hellesøe, Lykke-Hartmann Karin, Nissen Poul, Khandelia Himanshu, Poulsen Hanne
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.
Sci Rep. 2016 Feb 5;6:20442. doi: 10.1038/srep20442.
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.
动物细胞质膜上钠（Na⁺）和钾（K⁺）的重要梯度由钠钾ATP酶维持，这是一种αβ酶复合物，其α亚基负责离子转运和ATP水解。β亚基同工型的具体作用尚不清楚，不过β2对哺乳动物的运动生理学至关重要。在此，我们表明，与β1和β3相比，β2相对于向外开放的E2P状态稳定了Na⁺封闭的E1P状态，且该效应由其跨膜结构域介导。分子动力学模拟进一步证明，β跨膜螺旋的倾斜角度与其功能效应相关，这表明β的相对取向调节α亚基处的离子结合。β2主要在小脑的颗粒神经元和肾小球中表达，我们认为其独特的功能特性对于适当响应小脑的Na⁺和K⁺梯度很重要。
