• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nature >Pre-fusion structure of a human coronavirus spike protein
【24h】

Pre-fusion structure of a human coronavirus spike protein

机译：人冠状病毒刺突蛋白的融合前结构

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

HKU1 is a human betacoronavirus that causes mild yet prevalent respiratory disease1, and is related to the zoonotic SARS(2) and MERS3 betacoronaviruses, which have high fatality rates and pandemic potential. Cell tropism and host range is determined in part by the coronavirus spike (S) protein(4), which binds cellular receptors and mediates membrane fusion. As the largest known class I fusion protein, its size and extensive glycosylation have hindered structural studies of the full ectodomain, thus preventing a molecular understanding of its function and limiting development of effective interventions. Here we present the 4.0 resolution structure of the trimeric HKU1 S protein determined using singleparticle cryo-electron microscopy. In the pre-fusion conformation, the receptor-binding subunits, S1, rest above the fusion-mediating subunits, S2, preventing their conformational rearrangement. Surprisingly, the S1 C-terminal domains are interdigitated and form extensive quaternary interactions that occlude surfaces known in other coronaviruses to bind protein receptors. These features, along with the location of the two protease sites known to be important for coronavirus entry, provide a structural basis to support a model of membrane fusion mediated by progressive S protein destabilization through receptor binding and proteolytic cleavage. These studies should also serve as a foundation for the structure-based design of betacoronavirus vaccine immunogens.
机译：HKU1是一种人类β冠状病毒，可引起轻度但普遍的呼吸道疾病1，并且与人畜共患病的SARS（2）和MERS3β冠状病毒有关，它们具有很高的死亡率和大流行潜力。细胞的向性和宿主范围部分取决于冠状病毒刺突（S）蛋白（4），该蛋白结合细胞受体并介导膜融合。作为已知的最大的I类融合蛋白，其大小和广泛的糖基化阻碍了完整胞外域的结构研究，从而阻止了对其功能的分子理解并限制了有效干预措施的发展。在这里，我们介绍使用单粒子冷冻电子显微镜确定的三聚体HKU1 S蛋白的4.0分辨率结构。在融合前构象中，受体结合亚基S1位于融合介导亚基S2上方，从而阻止了它们的构象重排。出人意料的是，S1 C-末端结构域相互交叉并形成广泛的四级相互作用，该相互作用阻断了其他冠状病毒中已知的结合蛋白受体的表面。这些特征以及已知对冠状病毒进入很重要的两个蛋白酶位点的位置，为支持通过受体结合和蛋白水解裂解的渐进性S蛋白去稳定介导的膜融合模型提供了结构基础。这些研究也应作为基于结构设计β-冠状病毒疫苗免疫原的基础。

著录项

  • 来源
    《Nature》 |2016年第7592期|118-121|共4页
  • 作者

    Kirchdoerfer Robert N.; Cottrell Christopher A.; Wang Nianshuang; Pallesen Jesper; Yassine Hadi M.; Turner Hannah L.; Corbett Kizzmekia S.; Graham Barney S.; McLellan Jason S.; Ward Andrew B.;

  • 作者单位

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA;

    Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA;

    NIAID, Viral Pathogenesis Lab, Bldg 40,Room 2502,40 Convent Dr, Bethesda, MD 20892 USA|Qatar Univ, Biomed Res Ctr, QU NRC, Zone 5,Room D130, Doha, Qatar;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA;

    NIAID, Viral Pathogenesis Lab, Bldg 40,Room 2502,40 Convent Dr, Bethesda, MD 20892 USA;

    NIAID, Viral Pathogenesis Lab, Bldg 40,Room 2502,40 Convent Dr, Bethesda, MD 20892 USA;

    Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH 03755 USA;

    Scripps Res Inst, Dept Integrat Struct & Computat Biol, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号