Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Biochem Soc Trans. 2010 Oct;38(5):1349-55. doi: 10.1042/BST0381349.
Members within the paramyxovirus subfamily Paramyxovirinae constitute a large number of highly virulent human and animal pathogens. The glycoproteins present on these viruses are responsible for mediating host cell attachment and fusion and are key targets for the design of antiviral entry inhibitors. In the present review, we discuss recent structural studies which have led to a better understanding of the various mechanisms by which different paramyxoviruses use their attachment glycoproteins to hijack specific protein and glycan cell-surface receptors to facilitate viral entry. It is observed that the paramyxovirus attachment glycoprotein consists of a conserved overall structure which includes an N-terminal six-bladed β-propeller domain which is responsible for cell receptor binding. Crystal structures of this domain from different biomedically important paramyxoviruses, including measles, Nipah, Hendra, Newcastle disease and parainfluenza viruses, alone and in complex with their functional cell-surface receptors, demonstrate three contrasting mechanisms of receptor engagement that paramyxoviruses have evolved to confer discreet protein- and glycan-receptor specificity. This structural information highlights the adaptability of the paramyxovirus attachment glycoprotein surface and the potential for the emergence of new and potentially harmful viruses in human hosts.
副黏病毒亚科副黏病毒属中的成员构成了大量高度致病的人类和动物病原体。这些病毒表面存在的糖蛋白负责介导宿主细胞附着和融合，是设计抗病毒进入抑制剂的关键靶点。在本综述中，我们讨论了最近的结构研究，这些研究使我们更好地了解了不同副黏病毒利用其附着糖蛋白劫持特定蛋白和聚糖细胞表面受体以促进病毒进入的各种机制。观察到副黏病毒附着糖蛋白由保守的整体结构组成，包括负责细胞受体结合的 N 端六叶β-推进器结构域。来自不同具有重要生物医学意义的副黏病毒（包括麻疹、尼帕、亨德拉、新城疫和副流感病毒）的该结构域的晶体结构，单独存在或与它们的功能性细胞表面受体复合，展示了三种不同的受体结合机制，副黏病毒通过这些机制进化而来，赋予了对离散蛋白和聚糖受体的特异性。这些结构信息突出了副黏病毒附着糖蛋白表面的适应性，以及在人类宿主中出现新的潜在有害病毒的可能性。
