The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain
The role of proteolytic processing and the stable signal peptide in expression of the Old World arenavirus envelope glycoprotein ectodomain
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DOI：
10.1016/j.virol.2012.10.038
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发表时间：
2013-02-05
期刊：
影响因子：
3.7
通讯作者：
Kunz, Stefan
中科院分区：
文献类型：
--
作者：
Burri, Dominique J.;Pasquato, Antonella;Kunz, Stefan
沙粒病毒GP前体（GPC）的成熟涉及细胞信号肽酶和蛋白转化酶枯草菌素激酶同工酶1 (SKI-1)/位点1蛋白酶（S1P）的蛋白水解过程，产生由稳定信号肽（SSP）、受体结合GP1和融合活性跨膜GP2组成的三方复合物。本文研究了SKI-1/S1P加工和SSP在淋巴细胞性脉络丛脑膜炎病毒（LCMV）和拉沙病毒（LASV）重组GP外结构域生物合成中的作用。当在哺乳动物细胞中表达时，LCMV和LASV GP外畴由SKI-1/S1P加工，然后GP1和GP2分离。通过化学交联发现GP2外结构域自发形成三聚体。已知内源性SSP对全长沙粒病毒GPC的成熟和运输至关重要，但对于可溶性GP外结构域的加工和分泌是必不可少的，这表明SSP在全长沙粒病毒GPC的稳定预融合构象和运输中具有特定作用。(C) 2012爱思唯尔公司版权所有。
Maturation of the arenavirus GP precursor (GPC) involves proteolytic processing by cellular signal peptidase and the proprotein convertase subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P), yielding a tripartite complex comprised of a stable signal peptide (SSP), the receptor-binding GP1, and the fusion-active transmembrane GP2. Here we investigated the roles of SKI-1/S1P processing and SSP in the biosynthesis of the recombinant GP ectodomains of lymphocytic choriomeningitis virus (LCMV) and Lassa virus (LASV). When expressed in mammalian cells, the LCMV and LASV GP ectodomains underwent processing by SKI-1/S1P, followed by dissociation of GP1 from GP2. The GP2 ectodomain spontaneously formed trimers as revealed by chemical cross-linking. The endogenous SSP, known to be crucial for maturation and transport of full-length arenavirus GPC was dispensable for processing and secretion of the soluble GP ectodomain, suggesting a specific role of SSP in the stable prefusion conformation and transport of full-length GPC. (C) 2012 Elsevier Inc. All rights reserved.