The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine
The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine
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DOI：
10.1016/s0014-5793(02)03851-6
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发表时间：
2003-01-30
期刊：
影响因子：
3.5
通讯作者：
Rowlands, DJ
中科院分区：
文献类型：
--
作者：
Griffin, SDC;Beales, LP;Rowlands, DJ
丙型肝炎病毒（HCV）无法在体外生长，因此新药靶点的生化鉴定尤为重要。 HCV p7 是一种功能未知的小疏水蛋白，但对于相关病毒的颗粒感染性是必需的 [Harada, T. et al., (2000) J. Virol. 74、9498-9506]。我们证明 p7 可以在体内交联为六聚体。大肠杆菌表达的p7融合蛋白也在体外形成六聚体。这些和 HIS 标记的 p7 在黑色脂质膜中充当钙离子通道。这种活性被金刚烷胺消除，金刚烷胺是一种抑制流感离子通道的化合物 [Hay, A.J.等人。 (1985) EMBO J.4, 3021-3024;达夫，K.C.和 Ashley, R.H. (1992) Virology 190, 485-489]，最近被证明与当前的 HCV 疗法联合使用具有活性。 (C) 2002 年由 Elsevier Science B.V. 代表欧洲生化学会联合会出版。
Hepatitis C virus (HCV) cannot be grown in vitro, making biochemical identification of new drug targets especially important. HCV p7 is a small hydrophobic protein of unknown function, yet necessary for particle infectivity in related viruses [Harada, T. et al., (2000) J. Virol. 74, 9498-9506]. We show that p7 can be cross-linked in vivo as hexamers. Escherichia coli expressed p7 fusion proteins also form hexamers in vitro. These and HIS-tagged p7 function as calcium ion channels in black lipid membranes. This activity is abrogated by Amantadine, a compound that inhibits ion channels of influenza [Hay, A.J. et al. (1985) EMBO J. 4, 3021-3024; Duff, K.C. and Ashley, R.H. (1992) Virology 190, 485-489] and has recently been shown to be active in combination with current HCV therapies. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.