流感病毒通过多种动态相互作用结合其宿主细胞。
Influenza virus binds its host cell using multiple dynamic interactions.
机构信息
Department of Biology, Molecular Biophysics, Humboldt University Berlin, 10115 Berlin, Germany.
出版信息
Proc Natl Acad Sci U S A. 2012 Aug 21;109(34):13626-31. doi: 10.1073/pnas.1120265109. Epub 2012 Aug 6.
Abstract
Influenza virus belongs to a wide range of enveloped viruses. The major spike protein hemagglutinin binds sialic acid residues of glycoproteins and glycolipids with dissociation constants in the millimolar range [Sauter NK, et al. (1992) Biochemistry 31:9609-9621], indicating a multivalent binding mode. Here, we characterized the attachment of influenza virus to host cell receptors using three independent approaches. Optical tweezers and atomic force microscopy-based single-molecule force spectroscopy revealed very low interaction forces. Further, the observation of sequential unbinding events strongly suggests a multivalent binding mode between virus and cell membrane. Molecular dynamics simulations reveal a variety of unbinding pathways that indicate a highly dynamic interaction between HA and its receptor, allowing rationalization of influenza virus-cell binding quantitatively at the molecular level.
摘要
流感病毒属于广泛的包膜病毒。主要的刺突蛋白血凝素与糖蛋白和糖脂的唾液酸残基结合，解离常数在毫摩尔范围内 [Sauter NK，等。（1992）生物化学 31:9609-9621]，表明多价结合模式。在这里，我们使用三种独立的方法来描述流感病毒与宿主细胞受体的附着。基于光镊和原子力显微镜的单分子力谱显示出非常低的相互作用力。此外，连续解吸事件的观察强烈表明病毒和细胞膜之间存在多价结合模式。分子动力学模拟揭示了多种解吸途径，表明 HA 与其受体之间存在高度动态的相互作用，从而可以在分子水平上对流感病毒-细胞结合进行定量合理化。
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