Ion Binding and Selectivity of the Na+/H+ Antiporter MjNhaP1 from Experiment and Simulation.,The Journal of Physical Chemistry B

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Ion Binding and Selectivity of the Na+/H+ Antiporter MjNhaP1 from Experiment and Simulation.
The Journal of Physical Chemistry B ( IF 2.8 ) Pub Date : 2020-01-02 , DOI: 10.1021/acs.jpcb.9b08552
Judith Warnau _{1,

2} , David Wöhlert ₃ , Kei-Ichi Okazaki ₄ , Özkan Yildiz ₃ , Ana P Gamiz-Hernandez _{2,

5} , Ville R I Kaila _{2,

5} , Werner Kühlbrandt ₃ , Gerhard Hummer _{1,

6}

Affiliation

Cells employ membrane-embedded antiporter proteins to control their pH, salt concentration, and volume. The large family of cation/proton antiporters is dominated by Na+/H+ antiporters that exchange sodium ions against protons, but homologous K+/H+ exchangers have recently been characterized. We show experimentally that the electroneutral antiporter NhaP1 of Methanocaldococcus jannaschii (MjNhaP1) is highly selective for Na+ ions. We then characterize the ion selectivity in both the inward-open and outward-open states of MjNhaP1 using classical molecular dynamics simulations, free energy calculations, and hybrid quantum/classical (QM/MM) simulations. We show that MjNhaP1 is highly selective for binding of Na+ over K+ in the inward-open state, yet it is only weakly selective in the outward-open state. These findings are consistent with the function of MjNhaP1 as a sodium-driven deacidifier of the cytosol that maintains a high cytosolic K+ concentration in environments of high salinity. By combining experiment and computation, we gain mechanistic insight into the Na+/H+ transport mechanism and help elucidate the molecular basis for ion selectivity in cation/proton exchangers.

中文翻译：

通过实验和模拟，Na + / H +反转运蛋白MjNhaP1的离子结合和选择性。

细胞利用膜嵌入的反向转运蛋白来控制其pH，盐浓度和体积。阳离子/质子反转运蛋白的大家族主要是Na + / H +反转运蛋白，可将钠离子与质子交换，但是最近已对同源K + / H +交换剂进行了表征。我们实验表明，詹纳氏甲烷球菌的电中性反转运蛋白NhaP1（MjNhaP1）对Na +离子具有高度选择性。然后，我们使用经典的分子动力学模拟，自由能计算和混合量子/经典（QM / MM）模拟，在MjNhaP1的内向和外向开放状态下表征离子选择性。我们表明，MjNhaP1在向内开放状态下对Na +相对于K +的结合具有高度选择性，但在向外开放状态下仅具有较弱的选择性。这些发现与MjNhaP1作为细胞溶质的钠驱动脱酸剂的功能一致，该溶质在高盐度环境中保持高的胞浆K +浓度。通过将实验和计算相结合，我们获得了对Na + / H +传输机理的机械洞察力，并帮助阐明了阳离子/质子交换器中离子选择性的分子基础。

更新日期：2020-01-04

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