The Molecular Basis of Human IgG-Mediated Enhancement of C4b-Binding Protein Recruitment to Group A Streptococcus
The Molecular Basis of Human IgG-Mediated Enhancement of C4b-Binding Protein Recruitment to Group A Streptococcus
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DOI：
10.3389/fimmu.2019.01230
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发表时间：
2019-06-04
影响因子：
7.3
通讯作者：
Blom, Anna M.
中科院分区：
文献类型：
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作者：
Ermert, David;Laabei, Maisem;Blom, Anna M.
化脓性链球菌每年感染全世界超过7亿人。细菌采用的免疫逃避策略包括以人类特异性方式结合补体抑制剂、C4 b结合蛋白（C4 BP）和H因子。我们最近发现，人IgG增加了C4 BP与细菌表面的结合，这促进了链球菌的免疫逃避，并增加了小鼠的死亡率。我们试图确定IgG如何促进C4 BP与M蛋白家族成员蛋白H结合。蛋白H的二聚化对于增强与人C4 BP的结合是关键的。首先，我们说明了蛋白H，IgG和C4 BP形成了一个三方复合物。第二，表面等离子体共振显示蛋白H仅通过Fc而非Fab结构域结合IgG，并且具有高亲和力（IgG-蛋白H：K-D = 0.4 nM; IgG-Fc-蛋白H：K-D
Streptococcus pyogenes infects over 700 million people worldwide annually. Immune evasion strategies employed by the bacteria include binding of the complement inhibitors, C4b-binding protein (C4BP) and Factor H in a human-specific manner. We recently showed that human IgG increased C4BP binding to the bacterial surface, which promoted streptococcal immune evasion and increased mortality in mice. We sought to identify how IgG promotes C4BP binding to Protein H, a member of the M protein family. Dimerization of Protein H is pivotal for enhanced binding to human C4BP. First, we illustrated that Protein H, IgG, and C4BP formed a tripartite complex. Second, surface plasmon resonance revealed that Protein H binds IgG solely through Fc, but not Fab domains, and with high affinity (IgG-Protein H: K-D = 0.4 nM; IgG-Fc-Protein H: K-D