INTRODUCTION OF INTERSUBUNIT DISULFIDE BONDS IN THE MEMBRANE-DISTAL REGION OF THE INFLUENZA HEMAGGLUTININ ABOLISHES MEMBRANE-FUSION ACTIVITY
INTRODUCTION OF INTERSUBUNIT DISULFIDE BONDS IN THE MEMBRANE-DISTAL REGION OF THE INFLUENZA HEMAGGLUTININ ABOLISHES MEMBRANE-FUSION ACTIVITY
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DOI：
10.1016/0092-8674(92)90140-8
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发表时间：
1992-02-21
期刊：
影响因子：
64.5
通讯作者：
WHARTON, S
中科院分区：
文献类型：
--
作者：
GODLEY, L;PFEIFER, J;WHARTON, S
流感病毒血凝素（HA）介导病毒进入细胞低ph诱导膜融合事件内体。在融合的pH值下，整个HA长度发生了许多结构变化。为了探索它们的意义和它们对融合活性的必要性，我们制备了一个位点定向突变HA，它含有新的亚基间二硫键，旨在将三聚体的膜远端结构域共价交联。这些突变抑制了低ph诱导的构象变化，阻止了ha介导的膜融合；减少新型二硫键的条件恢复了膜融合活性。我们得出结论，透明质酸远端膜区的结构重排是膜融合活性所必需的。
Influenza virus hemagglutinin (HA) mediates viral entry into cells by a low pH-induced membrane fusion event in endosomes. A number of structural changes occur throughout the length of HA at the pH of fusion. To probe their significance and their necessity for fusion activity, we have prepared a site-directed mutant HA containing novel intersubunit disulfide bonds designed to cross-link covalently the membrane-distal domains of the trimer. These mutations inhibited the low pH-induced conformational changes and prevented HA-mediated membrane fusion; conditions that reduced the novel disulfide bonds restored membrane fusion activity. We conclude that structural rearrangements in the membrane distal region of the HA are required for membrane fusion activity.