Le Saux Agnès, Ng Patricia Miang Lon, Koh Joanne Jing Yun, Low Diana Hooi Ping, Leong Geraldine E-Ling, Ho Bow, Ding Jeak Ling
Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore.
J Mol Biol. 2008 Mar 28;377(3):902-13. doi: 10.1016/j.jmb.2008.01.045. Epub 2008 Jan 30.
Although the innate immune response is triggered by the formation of a stable assembly of pathogen-recognition receptors (PRRs) onto the pathogens, the driving force that enables this PRR-PRR interaction is unknown. Here, we show that serine proteases, which are activated during infection, participate in associating with the PRRs. Inhibition of serine proteases gravely impairs the PRR assembly. Using yeast two-hybrid and pull-down methods, we found that two serine proteases in the horseshoe crab Carcinoscorpius rotundicauda are able to bind to the following three core members of PRRs: galactose-binding protein, Carcinolectin-5 and C-reactive protein. These two serine proteases are (1) Factor C, which activates the coagulation pathway, and (2) C2/Bf, a protein from the complement pathway. By systematic molecular dissection, we show that these serine proteases interact with the core "pathogen-recognition complex" via their complement control protein modules.
尽管天然免疫反应是由病原体识别受体（PRRs）在病原体上形成稳定组装体所触发的，但促使这种PRR - PRR相互作用的驱动力尚不清楚。在这里，我们表明在感染过程中被激活的丝氨酸蛋白酶参与了与PRRs的结合。抑制丝氨酸蛋白酶会严重损害PRR组装。使用酵母双杂交和下拉方法，我们发现圆尾鲎（Carcinoscorpius rotundicauda）中的两种丝氨酸蛋白酶能够与PRRs的以下三个核心成员结合：半乳糖结合蛋白、Carcinolectin - 5和C反应蛋白。这两种丝氨酸蛋白酶分别是：（1）激活凝血途径的C因子，以及（2）补体途径中的一种蛋白质C2/Bf。通过系统的分子剖析，我们表明这些丝氨酸蛋白酶通过其补体控制蛋白模块与核心“病原体识别复合物”相互作用。
