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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus
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Structural basis for inhibition of complement C5 by the SSL7 protein from Staphylococcus aureus

机译：金黄色葡萄球菌的SSL7抑制补体C5的结构基础

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摘要

Staphylococcus aureus secretes the SSL7 protein as part of its immune evasion strategy. The protein binds both complement C5 and IgA, yet it is unclear whether SSL7 cross-links these two proteins and, if so, what purpose this serves the pathogen. We have isolated a stable lgA-SSL7-C5 complex, and our crystal structure of the C5-SSL7 complex confirms that binding to C5 occurs exclusively through the C-terminal β-grasp domain of S5L7 leaving the OB domain free to interact with IgA. SSL7 interacts with C5 >70 A from the C5a cleavage site without inducing significant conformational changes in C5, and efficient inhibition of convertase cleavage of C5 is shown to be IgA dependent. Inhibition of C5a production and bacteriolysis are all shown to require C5 and IgA binding while inhibition of hemolysis is achieved by the C5 binding SSL7 β-grasp domain alone. These results provide a conceptual and structural basis for the development of a highly specific complement inhibitor preventing only the formation of the lytic membrane attack complex without affecting the important signaling functions of C5a.
机译：金黄色葡萄球菌分泌SSL7蛋白是其免疫逃避策略的一部分。该蛋白结合补体C5和IgA，但是尚不清楚SSL7是否使这两个蛋白交联，如果这样，则该病原体有什么作用。我们已经分离出稳定的lgA-SSL7-C5复合物，并且我们的C5-SSL7复合物的晶体结构证实与C5的结合仅通过S5L7的C端β-抓结构域发生，而OB域却可以自由地与IgA相互作用。 SSL7与C5a切割位点的C5> 70 A相互作用，而不会引起C5的构象变化，并且有效抑制C5的转化酶切割是IgA依赖性的。抑制C5a产生和溶菌作用均显示需要C5和IgA结合，而溶血的抑制作用仅通过C5结合SSL7β-grasp域来实现。这些结果为开发高度特异性的补体抑制剂提供了概念和结构基础，所述补体抑制剂仅防止裂解膜攻击复合物的形成而不影响C5a的重要信号传导功能。

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  • 作者

    Nick S. Laursen; Natasha Gordon; Stefan Hermans; Natalie Lorenz; Nicola Jackson; Bruce Wines; Edzard Spillner; Jesper B. Christensen; Morten Jensen; Folmer Fredslund; Mette Bjerre; Lars Sottrup-Jensen; John D. Fraser; Gregers R. Andersen;

  • 作者单位

    Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus, Denmark;

    Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1020, New Zealand;

    Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1020, New Zealand;

    Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1020, New Zealand;

    Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1020, New Zealand;

    Centre for Immunology, Burnet Institute, Melbourne, Victoria 3004, Australia;

    Institute of Biochemistry and Food Sciences, Division of Biochemistry and Molecular Biology, University of Hamburg, 20146 Hamburg, Germany;

    Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus, Denmark;

    Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus, Denmark;

    Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus, Denmark;

    Immunoendocrine Research Unit, Medical Research Laboratories, Aarhus University Hospital, DK-8000 Aarhus, Denmark;

    Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus, Denmark;

    Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland 1020, New Zealand;

    Department of Molecular Biology, University of Aarhus, DK-8000 Aarhus, Denmark;

  • 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);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    crystallography; innate immunity; structural biology; complement; IgA;

    机译：晶体学先天免疫;结构生物学;补充;抗体;

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