The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg74
The orphan receptor C5L2 has high affinity binding sites for complement fragments C5a and C5a des-Arg74
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DOI：
10.1074/jbc.c100714200
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发表时间：
2002-03-01
影响因子：
4.8
通讯作者：
Monk, PN
中科院分区：
文献类型：
--
作者：
Cain, SA;Monk, PN
细胞对过敏性毒素C5a及其脱盐形式C5adR(74)的反应差异很大，这表明这些配体可能存在不止一种类型的细胞表面受体。然而，到目前为止，只有一种C5a和C5adR(74)的受体CD88被鉴定。在这里，我们报道了孤儿受体C5L2/gpr77，它与CD88有35%的氨基酸同源性，以高亲和力结合C5a，但与C5adR(74)的亲和力是CD88的10倍。C5L2对过敏毒素C3a也有中等的亲和力，但交叉竞争研究表明C3a与C5a结合在不同的位置。C4a能够取代C3a，提示C5L2和C3a受体一样，对这种过敏性毒素的结合亲和力较低。与CD88和C3a受体不同的是，C5L2不支持脱颗粒或增加细胞内[Ca~(2+)]，也不能对配体结合迅速内化。然而，用过敏毒素结扎C5L2确实通过百日咳毒素敏感的机制增强了对高亲和力IgE受体的交叉连接的脱颗粒反应。这些结果表明，C5L2是一种具有独特的配体结合和信号转导特性的过敏性毒素结合蛋白。
The substantial variations in the responses of cells to the anaphylatoxin C5a and its desarginated form, C5adR(74), suggest that more than one type of cell surface receptor for these ligands might exist. However, only a single receptor for C5a and C5adR(74), CD88, has been characterized to date. Here we report that the orphan receptor C5L2/gpr77, which shares 35% amino acid identity with CD88, binds C5a with high affinity but has a 10-fold higher affinity for C5adR(74) than CD88. C5L2 also has a moderate affinity for anaphylatoxin C3a, but cross-competition studies suggest that C3a binds to a distinct site from C5a. C4a was able to displace C3a, suggesting that C5L2, like the C3a receptor, may have a low binding affinity for this anaphylatoxin. Unlike CD88 and C3a receptor, C5L2 transfected into RBL-2H3 cells does not support degranulation or increases in intracellular [Ca2+] and is not rapidly internalized in response to ligand binding. However, ligation of C5L2 by anaphylatoxin did potentiate the degranulation response to cross-linkage of the high affinity IgE receptor by a pertussis toxin-sensitive mechanism. These results suggest that C5L2 is an anaphylatoxin-binding protein with unique ligand binding and signaling properties.