Reversible stages of the low-pH-triggered conformational change in influenza virus hemagglutinin
Reversible stages of the low-pH-triggered conformational change in influenza virus hemagglutinin
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DOI：
10.1093/emboj/cdf559
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发表时间：
2002-11-01
期刊：
影响因子：
11.4
通讯作者：
Chernomordik, LV
中科院分区：
文献类型：
--
作者：
Leikina, E;Ramos, C;Chernomordik, LV
在融合的pH值下，原型融合蛋白血凝素（HA）的再折叠被认为是负载弹簧的协调和不可逆放电，在初始和最终构象之间没有明显的中间产物。在这里，我们证明了HA再折叠涉及可逆构象，其寿命为几分钟。再中和后，低ph活化的HA从融合肽和HA2亚基的扭结环暴露，但HA1亚基尚未解离的构象中返回到与初始结构在功能、生化和免疫特性上没有区别的构象。从可逆构象到不可逆再折叠的转变速率取决于pH值和目标膜的存在。重要的是，初始构象的恢复被相邻HA三聚体之间的相互作用所阻断。确定的可逆再折叠阶段的存在对于允许多个HA副本同步释放构象能量至关重要，这是聚变所需要的。
The refolding of the prototypic fusogenic protein hemagglutinin (HA) at the pH of fusion is considered to be a concerted and irreversible discharge of a loaded spring, with no distinct intermediates between the initial and final conformations. Here, we show that HA refolding involves reversible conformations with a lifetime of minutes. After reneutralization, low pH-activated HA returns from the conformations wherein both the fusion peptide and the kinked loop of the HA2 subunit are exposed, but the HA1 subunits have not yet dissociated, to a structure indistinguishable from the initial one in functional, biochemical and immunological characteristics. The rate of the transition from reversible conformations to irreversible refolding depends on the pH and on the presence of target membrane. Importantly, recovery of the initial conformation is blocked by the interactions between adjacent HA trimers. The existence of the identified reversible stage of refolding can be crucial for allowing multiple copies of HA to synchronize their release of conformational energy, as required for fusion.