pH诱导的流感病毒M2蛋白C末端结构域的构象变化。
pH-induced conformational change of the influenza M2 protein C-terminal domain.
作者信息
Nguyen Phuong A, Soto Cinque S, Polishchuk Alexei, Caputo Gregory A, Tatko Chad D, Ma Chunlong, Ohigashi Yuki, Pinto Lawrence H, DeGrado William F, Howard Kathleen P
机构信息
Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, Pennsylvania 19081, USA.
出版信息
Biochemistry. 2008 Sep 23;47(38):9934-6. doi: 10.1021/bi801315m. Epub 2008 Aug 29.
Abstract
The M2 protein from influenza A is a pH-activated proton channel that plays an essential role in the viral life cycle and serves as a drug target. Using spin labeling EPR spectroscopy, we studied a 38-residue M2 peptide spanning the transmembrane region and its C-terminal extension. We obtained residue-specific environmental parameters under both high- and low-pH conditions for nine consecutive C-terminal sites. The region forms a membrane surface helix at both high and low pH, although the arrangement of the monomers within the tetramer changes with pH. Both electrophysiology and EPR data point to a critical role for residue Lys 49.
摘要
甲型流感病毒的M2蛋白是一种pH激活的质子通道，在病毒生命周期中起关键作用，也是一个药物靶点。利用自旋标记电子顺磁共振波谱技术，我们研究了一个跨越跨膜区及其C端延伸的38个残基的M2肽段。我们获得了九个连续C端位点在高pH和低pH条件下的残基特异性环境参数。尽管四聚体内单体的排列随pH变化，但该区域在高pH和低pH条件下均形成膜表面螺旋。电生理学和电子顺磁共振数据均表明残基赖氨酸49起着关键作用。
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