School of Marine Biosciences, Kitasato University, Okirai, Sanriku, Ofunato, Iwate 022-0101, Japan.
Glycobiology. 2011 Dec;21(12):1580-7. doi: 10.1093/glycob/cwr070. Epub 2011 May 24.
A skin mucus lectin exhibiting a homodimeric structure and an S-S bond between subunits of ~40 kDa was purified from flathead Platycephalus indicus (Scorpaeniformes). This lectin, named FHL (FlatHead Lectin), exhibited mannose-specific activity in a Ca(2+)-dependent manner. Although FHL showed no homology to any previously reported lectins, it did exhibit ~20% identity to previously discovered plasma kallikreins and coagulation factor XIs of mammals and Xenopus laevis. These known proteins are serine proteases and play pivotal roles in the kinin-generating system or the blood coagulation pathway. However, alignment analysis revealed that while FHL lacked a serine protease domain, it was homologous to the heavy-chain domain of plasma kallikreins and coagulation factor XI therefore suggesting that FHL is not an enzyme but rather a novel animal lectin. On the basis of this finding, we investigated the lectin activity of human plasma kallikrein and revealed that it could indeed act as a lectin. Other genes homologous to FHL were also found in the genome databases of some fish species, but not in mammals. In contrast, plasma kallikreins and coagulation factor XI have yet to be identified in fish. The present findings suggest that these mammalian enzymes may have originally emerged as a lectin and may have evolved into molecules with protease activity after separation from common ancestors.
从平头鲷（Scorpaeniformes）中纯化出一种具有同源二聚体结构和亚基间~40 kDa S-S 键的皮肤粘液凝集素。这种凝集素，命名为 FHL（平头凝集素），以 Ca(2+)-依赖性方式表现出甘露糖特异性活性。尽管 FHL 与以前报道的任何凝集素均无同源性，但它与已发现的哺乳动物和非洲爪蟾的血浆激肽释放酶和凝血因子 XI 具有约 20%的同一性。这些已知的蛋白质是丝氨酸蛋白酶，在激肽生成系统或血液凝固途径中发挥关键作用。然而，序列比对分析表明，尽管 FHL 缺乏丝氨酸蛋白酶结构域，但它与血浆激肽释放酶和凝血因子 XI 的重链结构域同源，因此表明 FHL 不是一种酶，而是一种新型动物凝集素。基于这一发现，我们研究了人血浆激肽释放酶的凝集素活性，并揭示它确实可以充当凝集素。在一些鱼类的基因组数据库中还发现了与 FHL 同源的其他基因，但在哺乳动物中没有。相比之下，鱼类中尚未鉴定出血浆激肽释放酶和凝血因子 XI。这些发现表明，这些哺乳动物酶可能最初是作为凝集素出现的，并且在与共同祖先分离后可能进化为具有蛋白酶活性的分子。
