Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function
Hic, a novel surface protein of Streptococcus pneumoniae that interferes with complement function
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DOI：
10.1074/jbc.m004572200
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发表时间：
2000-11-24
影响因子：
4.8
通讯作者：
Björck, L
中科院分区：
文献类型：
--
作者：
Janulczyk, R;Iannelli, F;Björck, L
重要的人类病原体肺炎链球菌从人血浆中吸收补体抑制剂因子H。我们在3型肺炎球菌的pspC位点发现了一种新的表面蛋白——补体因子h结合抑制剂（Hic）的编码基因，与其他血清型的pspC蛋白不同，Hic通过LPXTG基序固定在细胞壁上，并且与各种pspC蛋白的总体序列同源性较低。然而，nh2末端区域与几种PspC蛋白的nh2末端区域具有显著的同源性。覆盖该同源区域的Hic片段被表达为谷胱甘肽s -转移酶（GST）融合蛋白。GST:Hic（39-261）结合放射标记因子H并抑制因子H与不同血清型肺炎球菌的结合。用表面等离子体共振研究了GST:Hic（39-261）与因子H之间的相互作用动力学，结果表明GST:Hic（39-261）与因子H之间存在高亲和力结合(K-A = 5 × 10（7), K-D = 2.3 × 10(-8)）。缺乏Hic的突变型肺炎球菌在人血浆中没有对H因子的吸收，也没有与放射性标记的H因子结合，这表明Hic是3型肺炎球菌中H因子结合的原因。GST:Hic的存在并没有减弱H因子依赖性替代途径的抑制作用（39-261）。此外，Hic具有内在的抑制作用。
The important human pathogen Streptococcus pneumoniae was found to absorb factor H, an inhibitor of complement, from human plasma. We identified the gene encoding a novel surface protein, factor H-binding inhibitor of complement (Hic), in the pspC locus of type 3 pneumococci, Unlike PspC proteins in other serotypes, Hic is anchored to the cell wall by means of an LPXTG motif, and the overall sequence homology to various PspC proteins is low. However, the NH2-terminal region showed significant homology to the NH2-terminal region of several PspC proteins. A fragment of Hic, covering this homologous region, was expressed as a glutathione S-transferase (GST) fusion protein. GST:Hic(39-261) bound radiolabeled factor H and inhibited binding of factor H to pneumococci of different serotypes. Interaction kinetics between GST:Hic(39-261) and factor H were studied with surface plasmon resonance and showed a high affinity binding (K-A = 5 x 10(7), K-D = 2.3 x 10(-8)). Mutant pneumococci lacking Hic showed no absorption of factor H in human plasma and no binding of radiolabeled factor H, suggesting that Hic is responsible for factor H-binding in type 3 pneumococci, Factor H-dependent inhibition of the alternative pathway was not diminished by the presence of GST:Hic(39-261). I, addition, an intrinsic inhibitory effect of Hic is suggested.