Specific structural alteration of the influenza haemagglutinin by amantadine.
Specific structural alteration of the influenza haemagglutinin by amantadine.
复制标题
金刚烷胺对流感血凝素的特定结构改变。
作者：
R. Sugrue;Gulam Bahadur;M. Zambon;Marian Hall;Alan R. Douglas;Alan J. Hay
金刚烷胺盐酸盐特异性阻断病毒颗粒从H7流感病毒感染的细胞中释放。这似乎是金刚烷胺诱导血凝素（HA）改变为其低pH构象的直接结果。该作用是间接的，通过药物与M2蛋白的相互作用介导，因为单独在该组分中改变的突变体对金刚烷胺不敏感。药物作用的时间（合成后约15 - 20分钟）及其与蛋白水解裂解的一致性表明，HA的修饰发生在转运期间的晚期，但在插入质膜之前。由mM浓度的胺和0.1 μ M莫能菌素的抑制表明，金刚烷胺的作用引起囊内pH值的降低，这引发了HA的构象变化。因此，我们得出结论，金刚烷胺抑制的M2功能涉及抵消受感染细胞中胞吐途径的囊泡隔室的酸度，并且在保护酸敏感性糖蛋白的结构完整性方面很重要。
Amantadine hydrochloride specifically blocks the release of virus particles from H7 influenza virus infected cells. This appears to be the direct consequence of an amantadine induced change in the haemagglutinin (HA) to its low pH conformation. The effect is indirect and mediated via interaction of the drug with the M2 protein since mutants altered in this component alone are insensitive to amantadine. The timing of drug action, some 15‐20 min after synthesis, and its coincidence with proteolytic cleavage indicates that the modifications to HA occur late during transport but prior to insertion into the plasma membrane. Reversal by mM concentrations of amines and 0.1 microM monensin indicates that amantadine action causes a reduction in intravesicular pH which triggers the conformational change in HA. We conclude, therefore, that the function of M2 inhibited by amantadine is involved in counteracting the acidity of vesicular compartments of the exocytic pathway in infected cells and is important in protecting the structural integrity of the acid‐sensitive glycoprotein.