Gating mechanism of the influenza A M2 channel revealed by 1D and 2D IR spectroscopies.
Gating mechanism of the influenza A M2 channel revealed by 1D and 2D IR spectroscopies.
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DOI：
10.1016/j.str.2008.12.015
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发表时间：
2009-02-13
期刊：
影响因子：
--
通讯作者：
Arkin IT
中科院分区：
文献类型：
--
作者：
Manor J;Mukherjee P;Lin YS;Leonov H;Skinner JL;Zanni MT;Arkin IT
流感病毒中受pH控制的M2蛋白是病毒的关键成分，是氨基金刚烷抗流感药物阻断其H+通道活性的靶点。为了更好地了解其H+门控机制，我们用新的红外光谱和理论相结合的方法研究了脂质双层中的M2。用线性傅里叶变换红外光谱测定了主链的精确取向，用2D-IR光谱鉴定了通道衬里残留物。在低pH值(开态)下，我们的结果与先前发表的ss-核磁共振和X射线结构非常吻合。然而，在中性pH(闭合状态)下，我们的测量指出了一个很大的构象变化，这与跨膜α-螺旋旋转一个氨基酸登记一致：一种以前没有观察到的结构重排。结合同位素标记的FTIR和2D-IR光谱，以及模拟，提供了一种非侵入性的方法来询问膜蛋白的结构，特别是离子通道。
The pH-controlled M2 protein from Influenza is a critical component of the virus, serving as a target for aminoadamantane anti-flu agents that block its H+ channel activity. To better understand its H+-gating mechanism, we investigated M2 in lipid bilayers with a new combination of IR spectroscopies and theory. Linear FTIR spectroscopy was utilized to measure the precise orientation of the backbone carbonyl groups, and 2D-IR spectroscopy was utilized to identify channel-lining residues. At low pH (open-state), our results match previously published ss-NMR and X-ray structures remarkably well. However, at neutral pH (closed-state), our measurements point to a large conformational change, that is consistent with the transmembrane α-helices rotating by one amino acid register: a structural rearrangement not previously observed. The combination of isotope-labelled FTIR and 2D-IR spectroscopies, alongside simulations, provides a non-invasive mean of interrogating structures of membrane proteins in general and ion channels in particular.
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