MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing, China.
Biophys J. 2013 Dec 17;105(12):2714-23. doi: 10.1016/j.bpj.2013.11.006.
FocA belongs to the formate-nitrate transporter family and plays an essential role in the export and uptake of formate in organisms. According to the available crystal structures, the N-terminal residues of FocA are structurally featureless at physiological conditions but at reduced pH form helices to harbor the cytoplasmic entrance of the substrate permeation pathway, which apparently explains the cessation of electrical signal observed in electrophysiological experiments. In this work, we found by structural analysis and molecular dynamics simulations that those N-terminal helices cannot effectively preclude the substrate permeation. Equilibrium simulations and thermodynamic calculations suggest that FocA is permeable to both formate and formic acid, the latter of which is transparent to electrophysiological studies as an electrically neutral species. Hence, the cease of electrical current at acidic pH may be caused by the change of the transported substrate from formate to formic acid. In addition, the mechanism of formate export at physiological pH is discussed.
FocA 属于甲酸盐-硝酸盐转运体家族，在生物中外排和摄取甲酸盐方面发挥着重要作用。根据现有晶体结构，在生理条件下，FocA 的 N 端残基在结构上没有明显特征，但在降低的 pH 值下形成螺旋，以容纳底物渗透途径的细胞质入口，这显然解释了在电生理实验中观察到的电信号停止。在这项工作中，我们通过结构分析和分子动力学模拟发现，这些 N 端螺旋不能有效地阻止底物渗透。平衡模拟和热力学计算表明，FocA 对甲酸盐和甲酸都具有通透性，后者作为电中性物质在电生理研究中是透明的。因此，在酸性 pH 值下电流停止可能是由于转运的底物由甲酸盐变为甲酸。此外，还讨论了生理 pH 值下甲酸盐外排的机制。
