Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from influenza A virus
Backbone structure of the amantadine-blocked trans-membrane domain M2 proton channel from influenza A virus
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DOI：
10.1529/biophysj.106.090183
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发表时间：
2007-06-01
影响因子：
3.4
通讯作者：
Cross, Timothy A.
中科院分区：
文献类型：
--
作者：
Hu, Jun;Asbury, Tom;Cross, Timothy A.
已知金刚烷胺可阻断甲型流感病毒的 M2 质子通道。在这里，我们提出了用金刚烷胺封闭的 M2 跨膜结构域的结构，该结构是使用从固态 NMR 极化反转自旋交换魔角实验获得的取向约束构建的。数据表明单体中两个螺旋片段之间的扭结，相对于膜法线具有20度和31度的倾斜角。然后使用该单体结构构建四聚金刚烷胺阻断的 M2 跨膜通道的合理模型。还通过比较交叉偏振魔角旋转光谱观察了金刚烷胺结合的影响。此外，还显示了金刚烷胺抗性突变体 S31N 在存在和不存在金刚烷胺的情况下的光谱。
Amantadine is known to block the M2 proton channel of the Influenza A virus. Here, we present a structure of the M2 trans-membrane domain blocked with amantadine, built using orientational constraints obtained from solid-state NMR polarization-inversion-spin-exchange-at-the-magic-angle experiments. The data indicates a kink in the monomer between two helical fragments having 20 degrees and 31 degrees tilt angles with respect to the membrane normal. This monomer structure is then used to construct a plausible model of the tetrameric amantadine-blocked M2 trans-membrane channel. The influence of amantadine binding through comparative cross polarization magic-angle spinning spectra was also observed. In addition, spectra are shown of the amantadine-resistant mutant, S31N, in the presence and absence of amantadine.