Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Shanghai, China.
College of Fisheries and Life Science, Shanghai Ocean University, Shanghai, China.
FASEB J. 2019 Dec;33(12):13323-13333. doi: 10.1096/fj.201901142RR. Epub 2019 Sep 24.
Complement factor B/C2 family (Bf/C2F) proteins are core complement system components in vertebrates that are absent in invertebrates and have been lost by numerous species, raising evolutionary questions. At least 3 duplication events have occurred from Cnidaria (ancestor) to mammals. Type II Bf/C2 genes appeared during separation of Proterostomia and Deuterostomes. The second event occurred during separation of vertebrates and invertebrates, yielding type II-2 Bf/C2. The third event occurred when jawed and jawless fish were separated, eventually producing and genes. Herein, we report the second mollusc Bf/C2-type gene (). is similar to because both lack the first complement control protein module at the N terminus present in mammalian Bf/C2 proteins. Uniquely, the Ser protease (SP) module at the C terminus of ScBf is ∼50 aa longer than in other complement factor B/C2-type (Bf/C2T) proteins, and is Glu-rich. Bf/C2T proteins in molluscs lack the catalytic Ser in the SP module. Surprisingly, ScBf regulates rabbit erythrocyte agglutination, during which it is localized on the erythrocyte surface. Thus, ScBf may mediate the agglutination cascade and may be an upstream regulator of this process. Our findings provide new insight into the origin of the Bf/C2F.-Peng, M., Li, Z., Niu, D., Liu, X., Dong, Z., Li, J. Complement factor B/C2 in molluscs regulates agglutination and illuminates evolution of the Bf/C2 family.
补体因子 B/C2 家族（Bf/C2F）蛋白是脊椎动物中核心补体系统的组成部分，在无脊椎动物中不存在，并且已经在许多物种中丢失，这引发了进化问题。至少有 3 次复制事件发生在刺胞动物（祖先）到哺乳动物。II 型 Bf/C2 基因在原口动物和后口动物分离期间出现。第二次事件发生在脊椎动物和无脊椎动物分离期间，产生了 II-2 型 Bf/C2。第三次事件发生在有颌和无颌鱼类分离时，最终产生了 和 基因。在此，我们报道了第二种软体动物 Bf/C2 型基因（）。与 相似，因为两者都缺乏在哺乳动物 Bf/C2 蛋白中存在于 N 端的第一个补体控制蛋白模块。独特的是，ScBf 末端的 Ser 蛋白酶（SP）模块比其他补体因子 B/C2 型（Bf/C2T）蛋白长约 50 个氨基酸，并且富含 Glu。软体动物中的 Bf/C2T 蛋白缺乏 SP 模块中的催化 Ser。令人惊讶的是，ScBf 调节兔红细胞凝集，在此过程中它定位于红细胞表面。因此，ScBf 可能介导凝集级联反应，并且可能是该过程的上游调节剂。我们的研究结果为 Bf/C2F 的起源提供了新的见解。
