The conformation of the pore region of the M2 proton channel depends on lipid bilayer environment
The conformation of the pore region of the M2 proton channel depends on lipid bilayer environment
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DOI：
10.1110/ps.041185805
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发表时间：
2005-04-01
期刊：
影响因子：
8
通讯作者：
Howard, KP
中科院分区：
文献类型：
--
作者：
Duong-Ly, KC;Nanda, V;Howard, KP
来自甲型流感病毒的M2蛋白是一种由97个氨基酸组成的蛋白质，具有单个跨膜螺旋，可形成病毒功能所必需的质子选择性通道。M2蛋白的疏水性跨膜结构域（M2 TM）包含介导在膜环境中形成功能性四聚体的序列基序。先前已经提出了各种结构模型，其螺旋倾斜度不同，所提出的倾斜度范围从近似15度到38度。理解M2 TM结构的一个重要问题是肽-脂质相互作用在脂质双层结合四聚体稳定中的作用。在这里，我们标记的N末端的M2 TM与氮氧自由基和研究的四聚体重组成不同厚度的脂质双层，使用EPR光谱。光谱变化的分析提供的证据表明，脂质双层影响构象。M2 TM对膜组成的响应所显示的结构可塑性可能指示构象变化的功能要求。提出的各种结构模型M2 TM日期-每一个定义的一组不同的标准和在不同的环境-可能提供快照的不同的构象状态采样的蛋白质。
The M2 protein from influenza A virus is a 97-amino-acid protein with a single transmembrane helix that forms proton-selective channels essential to virus function. The hydrophobic transmembrane domain of the M2 protein (M2TM) contains a sequence motif that mediates the formation of functional tetramers in membrane environments. A variety of structural models have previously been proposed which differ in the degree of helix tilt, with proposed tilts ranging from similar to 15 degrees to 38 degrees. An important issue for understanding the structure of M2TM is the role of peptide-lipid interactions in the stabilization of the lipid bilayer bound tetramer. Here, we labeled the N terminus of M2TM with a nitroxide and studied the tetramer reconstituted into lipid bilayers of different thicknesses using EPR spectroscopy. Analyses of spectral changes provide evidence that the lipid bilayer does influence the conformation. The structural plasticity displayed by M2TM in response to membrane composition may be indicative of functional requirements for conformational change. The various structural models for M2TM proposed to date-each defined by a different set of criteria and in a different environment-might provide snapshots of the distinct conformational states sampled by the protein.