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首页> 外文期刊>Biochimica et biophysica acta. Biomembranes >Functional studies reveal the similarities and differences between AM2 and BM2 proton channels from influenza viruses
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Functional studies reveal the similarities and differences between AM2 and BM2 proton channels from influenza viruses

机译：功能研究揭示了来自流感病毒的AM2和BM2质子频道之间的相似性和差异

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Abstract AM2 and BM2 proton channels are attractive antiviral drug targets due to their essential roles during influenza virus replication. Although both AM2 and BM2 are proton-selective ion channels, they share little sequence similarity except for the HXXXW sequence, which suggests that their proton conductance properties might differ. To test this hypothesis, we applied two-electrode voltage clamp electrophysiological assays to study the specific conductance, leakage current, channel activation, and inhibition of AM2 and BM2 proton channels. It was found that BM2 channel has a higher specific conductance than AM2 channel at pH5.5. Unlike AM2 channel, whose proton conductance is asymmetric (from viral exterior to interior), BM2 channel is capable of conducting proton in both directions. Moreover, BM2 requires a more acidic pH for channel activation than AM2, as revealed by its lower p K a values. Finally, both AM2 and BM2 can be inhibited by Cu(II) and Cu(I). Overall, the results from this side-by-side comparison of AM2 and BM2 channels reveal the structure-function relationships of these two viroporins, and such information might be important for the designing of novel ion channels. Graphical abstract Display Omitted Highlights ? BM2 has a higher specific conductance than AM2 at pH5.5. ? BM2 has lower pKa values and requires lower pH for channel activation than AM2. ? BM2 shows outward leakage current while AM2 does not. ? Both BM2 and AM2 are inhibited by Cu(II) and Cu(I).
机译：摘要AM2和BM2质子频道是由于其在流感病毒复制过程中的基本作用引起的吸引力抗病毒药物靶标。虽然AM2和BM2都是质子选择性离子通道，但它们分享除HXXXW序列之外的序列相似度很小，这表明它们的质子电导属性可能不同。为了测试这一假设，我们应用了两电极电压钳电体神经测定以研究AM2和BM2质子通道的特定电导，漏电流，通道激活和抑制。发现BM2通道具有比PH5.5的am2通道更高的特定电导率。与AM2通道不同，其质子电导不对称（从病毒外部到内部），BM2通道能够在两个方向上传导质子。此外，BM2需要比AM2更酸性的pH值，而不是其低p k值。最后，可以通过Cu（II）和Cu（I）抑制AM2和BM2。总的来说，来自AM2和BM2通道的这种并排比较的结果揭示了这两种疾病的结构功能关系，并且这些信息对于设计新的离子通道可能是重要的。图形抽象显示省略了亮点？ BM2比PH5.5的am2更高的比电导。还BM2具有较低的PKA值，并且需要比AM2更低的通道激活pH值。还BM2显示出外侧漏电流，而AM2则不存在。还BM2和AM2都被Cu（II）和Cu（I）抑制。

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