Polyanion-induced self-association of complement factor H.
Polyanion-induced self-association of complement factor H.
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DOI：
10.4049/jimmunol.182.2.1061
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发表时间：
2009-01-15
期刊：
影响因子：
--
通讯作者：
Atkinson MA
中科院分区：
文献类型：
--
作者：
Pangburn MK;Rawal N;Cortes C;Alam MN;Ferreira VP;Atkinson MA
因子H是补体旁路途径活化的主要可溶性调节剂。当与C3 b和表面聚阴离子（如唾液酸、肝素和其他糖胺聚糖）结合时，可防止宿主细胞和组织上补体的活化。在这里，我们表明，与聚阴离子的相互作用导致自缔合形成的155，000 Da糖基化蛋白质的四聚体。单体人因子H是一种延伸的柔性蛋白，在不存在聚阴离子的凝胶过滤色谱法期间，相对于球状标准品，其表现出330，000 Da的表观大小。在硫酸葡聚糖（5，000 Da）或肝素存在下，表观分子量的中间物质700，000和一个有限的物种m.w.通过凝胶过滤观察到1，400，000。通过分析超离心的沉降平衡分析表明，在不存在聚阴离子的情况下，单体Mr为163，000，在存在小于2倍摩尔过量的硫酸葡聚糖的情况下，Mr为607，000，对应于四聚体。硫酸葡聚糖浓度的增加使因子H与酵母聚糖-C3 b的结合增加4.5倍。这是伴随着增加的衰变加速和辅因子活性的因子H对这些细胞。包含C-末端聚阴离子结合位点（补体控制蛋白结构域18-20）的表达片段也表现出聚阴离子诱导的自缔合，表明H因子的C-末端介导自缔合。结果表明，通过因子H识别宿主细胞和组织上的聚阴离子标记物，以及由此产生的补体激活调节，可能涉及因子H的二聚体和四聚体的形成。
Factor H is the primary soluble regulator of activation of the alternative pathway of complement. It prevents activation of complement on host cells and tissues upon association with C3b and surface polyanions such as sialic acids, heparin and other glycosaminoglycans. Here we show that interaction with polyanions causes self-association forming tetramers of the 155,000 Da glycosylated protein. Monomeric human factor H is an extended flexible protein that exhibits an apparent size of 330,000 Da, relative to globular standards, during gel filtration chromatography in the absence of polyanions. In the presence of dextran sulfate (5,000 Da) or heparin an intermediate species of apparent m.w. 700,000 and a limit species of m.w. 1,400,000 were observed by gel filtration. Sedimentation equilibrium analysis by analytical ultracentrifugation indicated a monomer Mr of 163,000 in the absence of polyanions and a Mr of 607,000, corresponding to a tetramer, in the presence of less than a 2-fold molar excess of dextran sulfate. Increasing concentrations of dextran sulfate increased binding of factor H to zymosan-C3b 4.5-fold. This was accompanied by an increase in both the decay accelerating and cofactor activity of factor H on these cells. An expressed fragment encompassing the C-terminal polyanion binding site (complement control protein domains 18–20) also exhibited polyanion-induced self association, suggesting that the C-terminal ends of factor H mediate self-association. The results suggest that recognition of polyanionic markers on host cells and tissues by factor H, and the resulting regulation of complement activation, may involve formation of dimers and tetramers of factor H.
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DOI：
10.1073/pnas.0501536102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Hageman, GS;Anderson, DH;Allikmets, R
通讯作者：
Allikmets, R
影响因子：
6.7
作者：
Kavanagh, David;Goodship, Timothy H. J.;Richards, Anna
通讯作者：
Richards, Anna
影响因子：
4.1
作者：
Kirkitadze, MD;Henderson, C;Barlow, PN
通讯作者：
Barlow, PN
影响因子：
4.4
作者：
Ferreira, Viviana P.;Herbert, Andrew P.;Pangburn, Michael K.
通讯作者：
Pangburn, Michael K.
影响因子：
11.4
作者：
Gaboriaud, C;Rossi, V;Fontecilla-Camps, JC
通讯作者：
Fontecilla-Camps, JC