Structural insights into the membrane fusion mechanism mediated by influenza virus hemagglutinin.
Structural insights into the membrane fusion mechanism mediated by influenza virus hemagglutinin.
复制标题
流感病毒血凝素介导的膜融合机制的结构见解。
DOI：
10.1021/bi401525h
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发表时间：
2014
期刊：
影响因子：
2.9
通讯作者：
Wang,Qinghua
中科院分区：
文献类型：
--
作者：
Ni,Fengyun;Chen,Xiaorui;Shen,Jun;Wang,Qinghua
膜融合涉及许多基本的细胞过程和包膜病毒进入宿主细胞。长期以来，A 型流感病毒 HA 一直作为通过酸性 pH 诱导的大规模结构重排进行蛋白质介导的膜融合机制研究的范例。在这里，我们报告了新确定的乙型流感病毒HA2在融合后状态的晶体结构。结合大量先前确定的甲型和乙型流感病毒 HA 的融合前结构以及甲型/H3N2 流感病毒 HA2 的融合后结构，我们确定了甲型和乙型流感病毒 HA 在构象转变中共有的保守特征，并记录了可能影响该过程详细机制的实质性差异。需要进一步的研究来剖析这些和其他结构差异对 HA 构象变化以及流感致病性和传播的影响，这可能最终加快新型抗流感融合抑制剂的发现。
Membrane fusion is involved in many fundamental cellular processes and entry of enveloped viruses into host cells. Influenza type A virus HA has long served as a paradigm for mechanistic studies of protein-mediated membrane fusion via large-scale structural rearrangements induced by acidic pH. Here we report the newly determined crystal structure of influenza B virus HA2in the postfusion state. Together with a large number of previously determined prefusion structures of influenza A and B virus HA and a postfusion structure of influenza A/H3N2 HA2, we identified conserved features that are shared between influenza A and B virus HA in the conformational transition and documented substantial differences that likely influence the detailed mechanisms of this process. Further studies are needed to dissect the effects of these and other structural differences in HA conformational changes and influenza pathogenicity and transmission, which may ultimately expedite the discovery of novel anti-influenza fusion inhibitors.