A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk.
A family of diverse Kunitz inhibitors from Echinococcus granulosus potentially involved in host-parasite cross-talk.
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DOI：
10.1371/journal.pone.0007009
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发表时间：
2009-09-17
期刊：
影响因子：
3.7
通讯作者：
Fernández C
中科院分区：
文献类型：
--
作者：
González S;Fló M;Margenat M;Durán R;González-Sapienza G;Graña M;Parkinson J;Maizels RM;Salinas G;Alvarez B;Fernández C
细粒棘球绦虫是包虫病/包虫病的病原体，非常适合其最终宿主。然而，幼虫蠕虫（原头节）在狗十二指肠中成功建立的分子机制尚不清楚。为了鉴定参与细粒棘球蚴-狗串扰的分子，我们调查了原头节和在 pH 2 下用胃蛋白酶处理的原头节的转录组。该分析鉴定了主要与胃蛋白酶/H+处理的蠕虫相关的分泌单域 Kunitz 蛋白的多基因家族，表明它们在感染开始时发挥作用。我们介绍了细粒棘球绦虫 Kunitz 家族的八个成员 (EgKU-1 – EgKU-8) 的相关分子特征。尽管多种多样，该家族包括三对密切的旁系同源物（EgKU-1/EgKU-4；EgKU-3/EgKU-8；EgKU-6/EgKU-7），它们可能是最近基因复制的产物。此外，我们描述了从幼虫中纯化 EgKU-1 和 EgKU-8，并提供数据表明该家族的一些成员（特别是 EgKU-3 和 EgKU-8）是由原头节分泌的。对天然 EgKU-1 和 EgKU-8 的详细动力学研究强调了它们的功能多样性。与大多数单域 Kunitz 蛋白一样，EgKU-8 是一种缓慢、紧密结合的丝氨酸蛋白酶抑制剂，与胰蛋白酶相比，其总体抑制常数 (K I *) 在皮摩尔范围内。与此形成鲜明对比的是，EgKU-1 不抑制任何所测定的肽酶。有趣的是，分子模型揭示了与 Kunitz 阳离子通道阻滞剂活性相关的结构元件。我们认为该抑制剂家族有可能作用于细粒棘球蚴-狗界面，并在感染的初始阶段干扰宿主的生理过程。
The cestode Echinococcus granulosus, the agent of hydatidosis/echinococcosis, is remarkably well adapted to its definitive host. However, the molecular mechanisms underlying the successful establishment of larval worms (protoscoleces) in the dog duodenum are unknown. With the aim of identifying molecules participating in the E. granulosus-dog cross-talk, we surveyed the transcriptomes of protoscoleces and protoscoleces treated with pepsin at pH 2. This analysis identified a multigene family of secreted monodomain Kunitz proteins associated mostly with pepsin/H+-treated worms, suggesting that they play a role at the onset of infection. We present the relevant molecular features of eight members of the E. granulosus Kunitz family (EgKU-1 – EgKU-8). Although diverse, the family includes three pairs of close paralogs (EgKU-1/EgKU-4; EgKU-3/EgKU-8; EgKU-6/EgKU-7), which would be the products of recent gene duplications. In addition, we describe the purification of EgKU-1 and EgKU-8 from larval worms, and provide data indicating that some members of the family (notably, EgKU-3 and EgKU-8) are secreted by protoscoleces. Detailed kinetic studies with native EgKU-1 and EgKU-8 highlighted their functional diversity. Like most monodomain Kunitz proteins, EgKU-8 behaved as a slow, tight-binding inhibitor of serine proteases, with global inhibition constants (K I *) versus trypsins in the picomolar range. In sharp contrast, EgKU-1 did not inhibit any of the assayed peptidases. Interestingly, molecular modeling revealed structural elements associated with activity in Kunitz cation-channel blockers. We propose that this family of inhibitors has the potential to act at the E. granulosus-dog interface and interfere with host physiological processes at the initial stages of infection.
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影响因子：
14.9
作者：
UniProt Consortium
通讯作者：
UniProt Consortium
影响因子：
4.8
作者：
Chand, HS;Schmidt, AE;Kisiel, W
通讯作者：
Kisiel, W
影响因子：
64.8
作者：
BELL, G;SMITH, JM
通讯作者：
SMITH, JM
影响因子：
4.8
作者：
Gasparini, S;Danse, JM;Ménez, A
通讯作者：
Ménez, A
影响因子：
1.9
作者：
Aguilar-Díaz, H;Bobes, RJ;Yánez, J
通讯作者：
Yánez, J