Identification and characterization of plasma kallikrein-kinin system inhibitors from salivary glands of the blood-sucking insect Triatoma infestans
Identification and characterization of plasma kallikrein-kinin system inhibitors from salivary glands of the blood-sucking insect Triatoma infestans
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DOI：
10.1111/j.1742-4658.2007.05958.x
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发表时间：
2007-08-01
期刊：
影响因子：
5.4
通讯作者：
Yuda, Masao
中科院分区：
文献类型：
--
作者：
Isawa, Harl;Orito, Yuki;Yuda, Masao
接吻虫 Triatoma infstans 唾液腺中的两种血浆激肽释放酶-激肽系统抑制剂已被鉴定和表征，分别命名为 triafestin-1 和 triafestin-2。重构实验表明，triafestin-1 和 triafestin-2 通过抑制因子 XII 和前激肽释放酶的相互激活以及随后的缓激肽释放来抑制激肽释放酶-激肽系统的激活。结合分析表明，triafestin-1 和 triafestin-2 以 Zn2+ 依赖性方式与因子 XII 和高分子量激肽原特异性相互作用，表明它们特异性识别 Zn2+ 诱导的因子 XII 和高分子量激肽原的构象变化。 Triafestin-1 和 triafestin-2 还抑制因子 XII 和高分子量激肽原与带负电荷的表面结合。此外，它们与因子 XII 的 N 末端和高分子量激肽原的结构域 D5 相互作用，这些是生物活化表面的结合结构域。这些结果表明，triafestin-1和triafestin-2通过干扰因子XII和高分子量激肽原与生物活化表面的结合来抑制激肽释放酶-激肽系统的活化，从而抑制昆虫吸血期间动物宿主中缓激肽的释放。
Two plasma kallikrein-kinin system inhibitors in the salivary glands of the kissing bug Triatoma infstans, designated triafestin-1 and triafestin-2, have been identified and characterized. Reconstitution experiments showed that triafestin-1 and triafestin-2 inhibit the activation of the kallikrein-kinin system by inhibiting the reciprocal activation of factor XII and prekallikrein, and subsequent release of bradykinin. Binding analyses showed that triafestin-1 and triafestin-2 specifically interact with factor XII and high molecular weight kininogen in a Zn2+ -dependent manner, suggesting that they specifically recognize Zn2+ -induced conformational changes in factor XII and high molecular weight kininogen. Triafestin-1 and triafestin-2 also inhibit factor XII and high molecular weight kininogen binding to negatively charged surfaces. Furthermore, they interact with both the N-terminus of factor XII and domain D5 of high molecular weight kininogen, which are the binding domains for biological activating surfaces. These results suggest that triafestin-1 and triafestin-2 inhibit activation of the kallikrein-kinin system by interfering with the association of factor XII and high molecular weight kininogen with biological activating surfaces, resulting in the inhibition of bradykinin release in an animal host during insect blood-feeding.