Carbohydrate recognition and complement activation by rat ficolin-B
Carbohydrate recognition and complement activation by rat ficolin-B
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DOI：
10.1002/eji.201040612
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发表时间：
2011-01-01
影响因子：
5.4
通讯作者：
Wallis, Russell
中科院分区：
文献类型：
--
作者：
Girija, Umakhanth Venkatraman;Mitchell, Daniel A.;Wallis, Russell
无花果蛋白酶是与PAMP和凋亡细胞上的结构结合的先天免疫组分。人类产生两种血清形式（L-和H-纤维胶凝蛋白）和白细胞相关形式（M-纤维胶凝蛋白），而啮齿动物和大多数其他哺乳动物产生纤维胶凝蛋白-A和-B，分别是L-和M-纤维胶凝蛋白的直向同源物。所有三种人纤维胶凝蛋白，连同小鼠和大鼠纤维胶凝蛋白-A，与甘露聚糖结合凝集素相关丝氨酸蛋白酶（MASP）结合并激活PAMP上补体的凝集素途径。相比之下，小鼠纤维胶凝蛋白-B不结合MASP并且不能激活补体。由于这些显着的差异，加上缺乏其他纤维胶凝蛋白-B的直系同源物的功能信息，我们的特点是大鼠纤维胶凝蛋白-B，并比较其物理和生化特性与其血清对应。数据显示，两种大鼠纤维胶凝蛋白均具有由三聚体亚基的寡聚体组成的原型结构。无花果蛋白酶-B主要识别唾液酸化糖，这是外源性和内源性配体的特征，而无花果蛋白酶-A具有令人惊讶的窄特异性，仅与测试的320种结构中的一种强烈结合：N-乙酰化三糖。令人惊讶的是，大鼠纤维胶凝蛋白-B活化的MASP-2与纤维胶凝蛋白-A相当。突变数据揭示小鼠纤维胶凝蛋白-B中活性的缺乏可能是由阻断纤维胶凝蛋白-MASP相互作用的推定MASP结合位点中的单个氨基酸变化引起的。
Ficolins are innate immune components that bind to PAMPs and structures on apoptotic cells. Humans produce two serum forms (L-and H-ficolin) and a leukocyte-associated form (M-ficolin), whereas rodents and most other mammals produce ficolins-A and -B, orthologues of L-and M-ficolin, respectively. All three human ficolins, together with mouse and rat ficolin-A, associate with mannan-binding lectin-associated serine proteases (MASPs) and activate the lectin pathway of complement on PAMPs. By contrast, mouse ficolin-B does not bind MASPs and cannot activate complement. Because of these striking differences together with the lack of functional information for other ficolin-B orthologues, we have characterized rat ficolin-B, and compared its physical and biochemical properties with its serum counterpart. The data show that both rat ficolins have archetypal structures consisting of oligomers of a trimeric subunit. Ficolin-B recognized mainly sialyated sugars, characteristic of exogenous and endogenous ligands, whereas ficolin-A had a surprisingly narrow specificity, binding strongly to only one of 320 structures tested: an N-acetylated trisaccharide. Surprisingly, rat ficolin-B activated MASP-2 comparable to ficolin-A. Mutagenesis data reveal that lack of activity in mouse ficolin-B is probably caused by a single amino acid change in the putative MASP-binding site that blocks the ficolin-MASP interaction.