Isawa Haruhiko, Orito Yuki, Jingushi Naruhiro, Iwanaga Siroh, Morita Akihiro, Chinzei Yasuo, Yuda Masao
Department of Medical Entomology, National Institute of Infectious Diseases, Tokyo, Japan.
FEBS J. 2007 Aug;274(16):4271-86. doi: 10.1111/j.1742-4658.2007.05958.x. Epub 2007 Jul 20.
Two plasma kallikrein-kinin system inhibitors in the salivary glands of the kissing bug Triatoma infestans, 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.
在侵扰锥猎蝽的唾液腺中已鉴定并表征了两种血浆激肽释放酶-激肽系统抑制剂，分别命名为锥猎蝽抑制素-1和锥猎蝽抑制素-2。重组实验表明，锥猎蝽抑制素-1和锥猎蝽抑制素-2通过抑制因子XII和前激肽释放酶的相互激活以及随后缓激肽的释放来抑制激肽释放酶-激肽系统的激活。结合分析表明，锥猎蝽抑制素-1和锥猎蝽抑制素-2以锌离子依赖的方式与因子XII和高分子量激肽原特异性相互作用，这表明它们特异性识别锌离子诱导的因子XII和高分子量激肽原的构象变化。锥猎蝽抑制素-1和锥猎蝽抑制素-2还抑制因子XII和高分子量激肽原与带负电荷表面的结合。此外，它们与因子XII的N端和高分子量激肽原的D5结构域相互作用，而这两个结构域是与生物活性表面结合的结构域。这些结果表明，锥猎蝽抑制素-1和锥猎蝽抑制素-2通过干扰因子XII和高分子量激肽原与生物活性表面的结合来抑制激肽释放酶-激肽系统的激活，从而在昆虫吸血过程中抑制动物宿主中缓激肽的释放。
