The structure of OMCI, a novel lipocalin inhibitor of the complement system
The structure of OMCI, a novel lipocalin inhibitor of the complement system
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DOI：
10.1016/j.jmb.2007.03.064
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发表时间：
2007-06-08
影响因子：
5.6
通讯作者：
Lea, Susan M.
中科院分区：
文献类型：
--
作者：
Roversi, Pietro;Lissina, Olga;Lea, Susan M.
补体（C）系统是一种有效的先天免疫防御系统，对寄生虫。我们最近表征并表达了OmCI，一种来源于软蜱Ornithodoros moubata的16 kDa蛋白，其特异性结合C5，从而防止C激活。在1.9埃分辨率下确定的重组OmCI的结构证实了脂质运载蛋白折叠，并揭示了该蛋白结合脂肪酸衍生物，我们已经通过质谱鉴定为蓖麻油酸。我们认为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。OmCI和其他具有不同功能的蜱脂质运载蛋白之间的序列差异的映射，结合OmCI活性的生物化学研究，支持OmCI通过阻止与C5转化酶的相互作用而不是通过阻断C5a切割位点起作用的假设。(c)2007爱思唯尔有限公司保留所有权利。
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 angstrom 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. (c) 2007 Elsevier Ltd. All rights reserved.