An amphioxus gC1q protein binds human IgG and initiates the classical pathway: Implications for a C1q-mediated complement system in the basal chordate
An amphioxus gC1q protein binds human IgG and initiates the classical pathway: Implications for a C1q-mediated complement system in the basal chordate
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DOI：
10.1002/eji.201444734
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发表时间：
2014-12-01
影响因子：
5.4
通讯作者：
Zhang, Shicui
中科院分区：
文献类型：
--
作者：
Gao, Zhan;Li, Mengyang;Zhang, Shicui
经典补体途径的起源在脊索动物进化过程中保持开放。BjC 1 q是一个C1 q样成员，在底脊索动物文昌鱼中被发现。它主要在肝盲肠、后肠和脊索中表达，并且在用细菌或脂磷壁酸和LPS攻击后显著上调。重组BjC 1 q及其球状头部结构域特异性地与脂磷壁酸和LPS相互作用，但BjC 1 q显示很少的凝集素活性。此外，rBjC 1 q可以组装形成结合蛋白酶C1 r/C1 s和补体激活所必需的高分子量寡聚体，并结合人C1 r/C1 s/甘露聚糖结合凝集素相关丝氨酸蛋白酶-2以及参与C4/C2切割和C3激活的文昌鱼丝氨酸蛋白酶。重要的是，rBjC 1 q与人IgG以及含有文昌鱼IG结构域的蛋白结合，导致经典补体途径的激活。这是第一次在无脊椎动物中发现C1 q样蛋白能够启动经典的补体途径，从而提高了文昌鱼具有C1 q介导的补体系统的可能性。它还提出了一个新的情况下出现的经典补体途径，在相反的建议，凝集素途径演变成经典途径。
The origin of the classical complement pathway remains open during chordate evolution. A C1q-like member, BjC1q, was identified in the basal chordate amphioxus. It is predominantly expressed in the hepatic caecum, hindgut, and notochord, and is significantly upregulated following challenge with bacteria or lipoteichoic acid and LPS. Recombinant BjC1q and its globular head domain specifically interact with lipoteichoic acid and LPS, but BjC1q displays little lectin activity. Moreover, rBjC1q can assemble to form the high molecular weight oligomers necessary for binding to proteases C1r/C1s and for complement activation, and binds human C1r/C1s/mannan-binding lectin-associated serine protease-2 as well as amphioxus serine proteases involved in the cleavage of C4/C2, and C3 activation. Importantly, rBjC1q binds with human IgG as well as an amphioxus Ig domain containing protein, resulting in the activation of the classical complement pathway. This is the first report showing that a C1q-like protein in invertebrates is able to initiate classical pathway, raising the possibility that amphioxus possesses a C1q-mediated complement system. It also suggests a new scenario for the emergence of the classical complement pathway, in contrast to the proposal that the lectin pathway evolved into the classical pathway.