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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957
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Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957

机译：血凝素形成的受体复合物的结构，1957年亚洲大流行性流感

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摘要

The viruses that caused the three influenza pandemics of the twentieth century in 1918, 1957, and 1968 had distinct hemagglu-tinin receptor binding glycoproteins that had evolved the capacity to recognize human cell receptors. We have determined the structure of the H2 hemagglutinin from the second pandemic, the "Asian Influenza" of 1957. We compare it with the 1918 "Spanish Influenza" hemagglutinin, H1, and the 1968 "Hong Kong Influenza" hemagglutinin, H3, and show that despite its close overall structural similarity to H1, and its more distant relationship to H3, the H2 receptor binding site is closely related to that of H3 hemagglutinin. By analyzing hemagglutinins of potential H2 avian precursors of the pandemic virus, we show that the human receptor can be bound by avian hemagglutinins that lack the human-specific mutations of H2 and H3 pandemic viruses, Gln-226Leu, and Gly-228Ser. We show how Gln-226 in the avian H2 receptor binding site, together with Asn-186, form hydrogen bond networks through bound water molecules to mediate binding to human receptor. We show that the human receptor adopts a very similar conformation in both human and avian hemagglutinin-receptor complexes. We also show that Leu-226 in the receptor binding site of human virus hemagglutinins creates a hydrophobic environment near the Sia-1-Gal-2 glycosidic linkage that favors binding of the human receptor and is unfavorable for avian receptor binding. We consider the significance for the development of pandemics, of the existence of avian viruses that can bind to both avian and human receptors.
机译：在1918年，1957年和1968年导致20世纪三大流感大流行的病毒具有独特的血凝素-肌动蛋白受体结合糖蛋白，这些蛋白已经发展了识别人类细胞受体的能力。我们从第二次大流行的1957年“亚洲流感”中确定了H2血凝素的结构。将其与1918年的“西班牙流感”血凝素H1和1968年的“香港流感”血凝素H3进行了比较，并显示尽管它与H1的总体结构相似，并且与H3的关系更远，但H2受体的结合位点与H3血凝素的结合位点密切相关。通过分析大流行病毒潜在H2禽前体的血凝素，我们显示人受体可以被缺乏H2和H3大流行病毒，Gln-226Leu和Gly-228Ser的人特异性突变的禽血凝素结合。我们展示了禽H2受体结合位点中的Gln-226与Asn-186一起如何通过结合的水分子形成氢键网络来介导与人类受体的结合。我们表明，人类受体在人类和禽血凝素受体复合物中均采用非常相似的构象。我们还显示，在人类病毒血凝素受体结合位点上的Leu-226在Sia-1-Gal-2糖苷键附近产生了疏水环境，有利于人类受体的结合，不利于禽类受体的结合。我们考虑了对大流行病的发展的重要性，即存在可以与禽和人类受体结合的禽病毒。

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    Junfeng Liu; David J. Stevens; Lesley F. Haire; Philip A. Walker; Peter J. Coombs; Rupert J. Russell; Steven J. Gamblin; John J. Skehel;

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    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom;

    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom;

    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom;

    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom;

    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom;

    Interdisciplinary Centre for Human and Avian Influenza Research, School of Biology, University of St. Andrews, Fife KY16 9ST, United Kingdom;

    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom;

    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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