Identification and characterization of onchoastacin, an astacin-like metalloproteinase from the filaria Onchocerca volvulus
Identification and characterization of onchoastacin, an astacin-like metalloproteinase from the filaria Onchocerca volvulus
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DOI：
10.1016/j.micinf.2007.01.007
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发表时间：
2007-04-01
影响因子：
5.8
通讯作者：
Brattig, Norbert W.
中科院分区：
文献类型：
--
作者：
Borchert, Nadine;Becker-Pauly, Christoph;Brattig, Norbert W.
组织侵入性线虫盘尾丝虫引起人类盘尾丝虫病的皮肤和眼睛病理。成年雌虫在皮下结节中固着，微丝蚴从结节中大量释放，雄虫和幼蠕虫通过宿主组织迁移。基质降解金属和丝氨酸蛋白酶已被检测到排泄分泌蠕虫产品，可能是必不可少的迁移的移动的阶段。本研究中，我们克隆了一个1713 bp的艾奥纳cDNA，编码一种O.肠扭转已被隔离。预测的蛋白质序列包括指示分泌到细胞外空间的信号肽、前肽、虾红素样蛋白酶结构域、EGF样和CUB结构域，从而将蛋白质鉴定为锌内肽酶的虾红素家族的成员。Onchoastacin，Ov-AST-1，与包括小杆线虫和钩虫属的线虫astacin的亚家族最密切相关。Ov-AST-I在杆状病毒感染的昆虫细胞中表达为重组蛋白，并表现出酶活性。通过证明IgG与重组Ov-AST-1和与蛋白质的两个肽反应来指示盘曲霉素对宿主免疫系统的暴露。由于同源金属蛋白酶是一种有前途的钩虫疫苗的一部分，Ov-AST-1可能是丝虫感染干预策略的候选者。(c)2007年，Elsevier Masson SAS。All rights reserved.
The tissue-invasive nematode Onchocerca volvulus causes skin and eye pathology in human Onchocerciasis. While the adult females reside sessile in subcutaneous nodules, the microfilariae are abundantly released from the nodules, males and juvenile worms migrate through the host tissue. Matrix-degrading metallo- and serine proteinases have been detected in excretory-secretory worm products that may be essential for migration of the mobile stages. In this study, a 1713 bp Iona cDNA encoding for a putative proteinase of O. volvulus has been isolated. The predicted protein sequence includes a signal peptide indicating secretion to the extracellular space, a propeptide, an astacin-like protease domain, an EGF-like and a CUB-domain, thereby identifying the protein as a member of the astacin family of zinc endopeptidases. Onchoastacin, Ov-AST-1, is most closely related to a subfamily comprising nematode astacins including Caenorhabditis and Ancylostoma. Ov-AST-I was expressed as a recombinant protein in baculovirus-infected insect cells and exhibited enzymatic activity. The exposure of onchoastacin to the host immune system is indicated by demonstration of IgG reacting with the recombinant Ov-AST-1 and with two peptides of the protein. Since a homologous metalloproteinase is part of a promising hookworm vaccine, Ov-AST-1 may be a candidate for intervention strategies in filarial infections. (c) 2007 Elsevier Masson SAS. All rights reserved.