The Toxoplasma adhesive protein MIC2 is proteolytically processed at multiple sites by two parasite-derived proteases
The Toxoplasma adhesive protein MIC2 is proteolytically processed at multiple sites by two parasite-derived proteases
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DOI：
10.1074/jbc.275.19.14346
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发表时间：
2000-05-12
影响因子：
4.8
通讯作者：
Sibley, LD
中科院分区：
文献类型：
--
作者：
Carruthers, VB;Sherman, GD;Sibley, LD
MIC2是一种黏附蛋白，参与专性细胞内寄生虫刚地弓形虫对宿主细胞的入侵。早期研究表明，MIC2由细胞外寄生虫分泌到培养基中，且释放过程与蛋白水解修饰同时发生。由于对刚地弓形虫分泌的蛋白质的蛋白水解加工了解甚少，我们开展了这项研究以探究伴随MIC2分泌的蛋白水解事件。我们证明当MIC2释放到培养上清液中时，其C末端结构域被一种称为MPP1的蛋白酶去除。此外，在释放之前，第二种称为MPP2的蛋白酶修剪MIC2的N末端，导致释放出大小不均的MIC2种类。尽管MPP1的活性不受所测试的任何蛋白酶抑制剂的影响，但MPP2的活性被一组丝氨酸和半胱氨酸蛋白酶抑制剂所阻断。这些结果表明，MIC2在多个位点被两种可能在寄生虫表面起作用的不同酶进行蛋白水解修饰。
MIC2 is an adhesive protein that participates in host cell invasion by the obligate intracellular parasite Toxoplasma gondii, Earlier studies established that MIC2 is secreted into the culture medium by extracellular parasites and that release is coincident with proteolytic modification. Since little is known about proteolytic processing of proteins secreted by T. gondii, we undertook this study to investigate the proteolytic events that accompany secretion of MICE. We demonstrate that the C-terminal domain of MICE is removed by a protease, termed MPP1, when MIC2 is released into the culture supernatant. Additionally, prior to release, a second protease, termed MPP2, trims the N terminus of MIC2, resulting in the release of heterogeneously sized species of MIC2. Although MPP1 activity was unaffected by any of the protease inhibitors tested, MPP2 activity was blocked by a subset of serine and cysteine protease inhibitors. These results establish that MIC2 is proteolytically modified at multiple sites by two distinct enzymes that probably operate on the parasite surface.