Schistosome invasion of human skin and degradation of dermal elastin are mediated by a single serine protease
Schistosome invasion of human skin and degradation of dermal elastin are mediated by a single serine protease
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DOI：
10.1074/jbc.m006997200
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发表时间：
2000-12-08
影响因子：
4.8
通讯作者：
McKerrow, JH
中科院分区：
文献类型：
--
作者：
Salter, JP;Lim, KC;McKerrow, JH
曼氏血吸虫（Schistosoma mansoni）的水生幼虫（尾蚴）通过降解包括弹性蛋白在内的宿主蛋白质而迅速穿透人类皮肤。已提出涉及两种丝氨酸蛋白酶，一种是糜蛋白酶样蛋白酶，第二种是胰蛋白酶样蛋白酶。为了评估这两种蛋白酶在幼虫入侵中的相对作用，对它们进行了纯化，序列鉴定，然后进行了生化表征。胰蛋白酶样活性被分解为两种不同的丝氨酸蛋白酶，在预测的氨基酸序列中76%相似，Southern印迹分析，基因组聚合酶链反应和免疫定位证明胰蛋白酶样蛋白酶实际上不是来自于螺旋体，而是与蜗牛宿主光滑双脐螺的幼虫一起释放的，使用选择性抑制剂的侵袭抑制试验证实，胰凝乳蛋白酶样蛋白酶是参与皮肤渗透的酶。它降解皮肤弹性蛋白的能力得到了证实，弹性蛋白内的三个切割位点有助于定义一个新的弹性蛋白酶家族。
Aquatic larvae (cercariae) of the trematode parasite Schistosoma mansoni rapidly penetrate human skin by degrading host proteins including elastin, Two serine proteases, one chymotrypsin-like and the second trypsin-like, have been proposed to be involved. To evaluate the relative roles of these two proteases in larval invasion, both were purified, identified by sequence, and then biochemically characterized. The trypsin-like activity was resolved into two distinct serine proteases 76% similar in predicted amino acid sequence, Southern blot analysis, genomic polymerase chain reaction, and immunolocalization demonstrated that the trypsin-like proteases are in fact not from the schistosome, but are released with larvae from the snail host Biomphalaria glabrata, Invasion inhibition assays using selective inhibitors confirmed that the chymotrypsin-like protease is the enzyme involved in skin penetration. Its ability to degrade skin elastin was confirmed, and the three sites of cleavage within elastin help define a new family of elastases.