Analogous interactions in initiating complexes of the classical and lectin pathways of complement.
Analogous interactions in initiating complexes of the classical and lectin pathways of complement.
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DOI：
10.4049/jimmunol.0900666
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Wallis R
中科院分区：
文献类型：
--
作者：
Phillips AE;Toth J;Dodds AW;Girija UV;Furze CM;Pala E;Sim RB;Reid KB;Schwaeble WJ;Schmid R;Keeble AH;Wallis R
补体激活的经典途径和凝集素途径可中和病原体并刺激关键的免疫过程。这两种途径都是由与特定丝氨酸蛋白酶相关的含胶原蛋白的可溶性模式识别分子启动的。在经典途径中，C1 q与抗体-抗原复合物或细菌表面结合以激活C1 r和C1 s。在凝集素途径中，甘露聚糖结合凝集素（MBL）和纤维胶凝蛋白结合病原体上的碳水化合物以活化MASP-2。为了解释导致经典途径激活的相互作用，我们分析了人类C1 q，C1 r和C1 s之间的结合，这些结合形成C1，使用全长和截短的蛋白酶组分。我们发现，C1 r和C1 s结合C1 q独立。CUB 1-EGF片段对结合的贡献最大，但C1 r的CUB 2也很重要，而C1 s的CUB 2则不重要。每个C1 rs四聚体呈现总共六个结合位点，每个C1 q的胶原结构域一个。我们还表明，凝集素和经典途径的子组件交叉相互作用。因此，虽然复合物的化学计量不同，相互作用是类似的，与识别和蛋白酶子组件之间的等效接触。重要的是，这些新数据与现有的C1模型相反，并使我们能够提出一个新的模型，使用MBL-MASP相互作用作为模板。
The classical and lectin pathways of complement activation neutralise pathogens and stimulate key immunological processes. Both pathways are initiated by collagen-containing, soluble pattern-recognition molecules associated with specific serine proteases. In the classical pathway, C1q binds to antibody-antigen complexes or bacterial surfaces to activate C1r and C1s. In the lectin pathway, mannan-binding lectin (MBL) and ficolins bind to carbohydrates on pathogens to activate MASP-2. To characterise the interactions leading to classical pathway activation, we have analysed binding between human C1q, C1r and C1s, which associate to form C1, using full-length and truncated protease components. We show that C1r and C1s bind to C1q independently. The CUB1-EGF fragments contribute most towards binding, but CUB2 of C1r, but not of C1s, is also important. Each C1rs tetramer presents a total of six binding sites, one for each of the collagenous domains of C1q. We also demonstrate that subcomponents of the lectin and classical pathways cross-interact. Thus, although the stoichiometries of complexes differ, interactions are analogous, with equivalent contacts between recognition and protease subcomponents. Importantly, these new data are contrary to existing models of C1, and enable us to propose a new model, using MBL-MASP interactions as a template.
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DOI：
10.1073/pnas.0402180101
发表时间：
2004-07-06
影响因子：
11.1
作者：
Matsushita, M;Matsushita, A;Fujita, T
通讯作者：
Fujita, T
影响因子：
4.8
作者：
Gaboriaud, C;Juanhuix, J;Arlaud, GJ
通讯作者：
Arlaud, GJ
影响因子：
5.6
作者：
Li, W;Keeble, AH;Kleanthous, C
通讯作者：
Kleanthous, C
影响因子：
2.8
作者：
Gaboriaud, Christine;Teillet, Florence;Arlaud, Gerard J.
通讯作者：
Arlaud, Gerard J.
影响因子：
5.6
作者：
Harmat, V;Gál, P;Závodszky, P
通讯作者：
Závodszky, P