Roversi Pietro, Lissina Olga, Johnson Steven, Ahmat Nurfilza, Paesen Guido C, Ploss Kerstin, Boland Wilhelm, Nunn Miles A, Lea Susan M
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, England, UK.
J Mol Biol. 2007 Jun 8;369(3):784-93. doi: 10.1016/j.jmb.2007.03.064. Epub 2007 Mar 30.
The complement (C) system is a potent innate immune defence system against parasites. We have recently characterised and expressed OmCI, a 16 kDa protein derived from the soft tick Ornithodoros moubata that specifically binds C5, thereby preventing C activation. The structure of recombinant OmCI determined at 1.9 A resolution confirms a lipocalin fold and reveals that the protein binds a fatty acid derivative that we have identified by mass spectrometry as ricinoleic acid. We propose that OmCI could sequester one of the fatty acid-derived inflammatory modulators from the host plasma, thereby interfering with the host inflammatory response to the tick bite. Mapping of sequence differences between OmCI and other tick lipocalins with different functions, combined with biochemical investigations of OmCI activity, supports the hypothesis that OmCI acts by preventing interaction with the C5 convertase, rather than by blocking the C5a cleavage site.
补体（C）系统是抵御寄生虫的强大先天性免疫防御系统。我们最近对源自软蜱钝缘蜱的一种16 kDa蛋白OmCI进行了表征和表达，该蛋白特异性结合C5，从而阻止补体激活。以1.9 Å分辨率测定的重组OmCI结构证实了其脂钙蛋白折叠，并揭示该蛋白结合了一种脂肪酸衍生物，我们通过质谱鉴定为蓖麻油酸。我们提出，OmCI可以从宿主血浆中隔离一种脂肪酸衍生的炎症调节剂，从而干扰宿主对蜱叮咬的炎症反应。对OmCI与其他具有不同功能的蜱脂钙蛋白之间的序列差异进行图谱分析，并结合对OmCI活性的生化研究，支持了OmCI通过阻止与C5转化酶相互作用而发挥作用的假说，而不是通过阻断C5a裂解位点。
