Functional characterization of BbCRASP-2, a distinct outer membrane protein of Borrelia burgdorferi that binds host complement regulators factor H and FHL-1
Functional characterization of BbCRASP-2, a distinct outer membrane protein of Borrelia burgdorferi that binds host complement regulators factor H and FHL-1
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DOI：
10.1111/j.1365-2958.2006.05318.x
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发表时间：
2006-09-01
影响因子：
3.6
通讯作者：
Kraiczy, Peter
中科院分区：
文献类型：
--
作者：
Hartmann, Kristina;Corvey, Carsten;Kraiczy, Peter
伯氏疏螺旋体，莱姆病的病原，采用复杂的手段在不同的哺乳动物宿主中生存。最近的研究表明，获得补体调节因子H和因子H样蛋白-1 （FHL-1）可以使螺旋体抵抗补体介导的杀伤。血清耐药伯氏疏螺旋体表达多达五种不同的补体调节获得表面蛋白（CRASPs），结合因子H和/或FHL-1。在这项研究中，我们已经鉴定并表征了其中一个伯氏疏螺旋体蛋白，命名为BbCRASP-2。BbCRASP-2不同于先前鉴定的四种伯氏疏螺旋体菌株的因子H/ fhl -1结合crasp。编码BbCRASP-2基因的单拷贝cspZ位于线性质粒lp28-3上。BbCRASP-2与因子H/ fhl -1结合蛋白BbCRASP-1以及因子H结合Erp （OspE/ f相关）蛋白家族成员高度分化。肽图谱分析显示因子H/FHL-1结合位点不连续，发现c端截断使因子H与FHL-1的结合失效。两种宿主补体调节因子的主要BbCRASP-2结合位点被定位到短共识重复7 （scr7）。与BbCRASP-2结合的因子H和FHL-1维持因子i介导的C3b失活的辅因子活性，并加速C3转化酶的衰变。在血清敏感的伯氏疏螺旋体突变体B313中，BbCRASP-2的表达增加了对补体介导裂解的抗性。BbCRASP-2的表征现在提供了伯氏疏螺旋体三种不同补体调节结合蛋白家族的完整图像，为莱姆病的发病机制提供了新的见解。
Borrelia burgdorferi, the aetiological agent of Lyme disease, employs sophisticated means to survive in diverse mammalian hosts. Recent studies demonstrated that acquisition of complement regulators factor H and factor H-like protein-1 (FHL-1) allows spirochetes to resist complement-mediated killing. Serum-resistant B. burgdorferi express up to five distinct complement regulator-acquiring surface proteins (CRASPs) that bind factor H and/or FHL-1. In this study we have identified and characterized one of those B. burgdorferi proteins, named BbCRASP-2. BbCRASP-2 is distinct from the four previously identified factor H/FHL-1-binding CRASPs of B. burgdorferi strains. The single copy of the gene encoding BbCRASP-2, cspZ, is located on the linear plasmid lp28-3. BbCRASP-2 is highly divergent from the factor H/FHL-1-binding protein BbCRASP-1 and from members of the factor H-binding Erp (OspE/F-related) protein family. Peptide mapping analysis revealed that the factor H/FHL-1 binding site is discontinuous and it was found that C-terminal truncations abrogate factor H and FHL-1 binding. The predominant BbCRASP-2 binding site of both host complement regulators was mapped to the short consensus repeat 7 (SCR 7). Factor H and FHL-1 bound to BbCRASP-2 maintain cofactor activity for factor I-mediated C3b inactivation and accelerate the decay of the C3 convertase. Expression of BbCRASP-2 in serum-sensitive B. burgdorferi mutant B313 increased resistance to complement-mediated lysis. The characterization of BbCRASP-2 now provides a complete picture of the three diverse complement regulator-binding protein families of B. burgdorferi yielding new insights into the pathogenesis of Lyme disease.