Mapping the landscape of the lymphocytic choriomeningitis virus stable signal peptide reveals novel functional domains.
Mapping the landscape of the lymphocytic choriomeningitis virus stable signal peptide reveals novel functional domains.
复制标题
绘制淋巴细胞脉络丛脑膜炎病毒稳定信号肽的图谱揭示了新的功能域。
DOI：
10.1128/jvi.02759-06
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发表时间：
2007
影响因子：
5.4
通讯作者：
Buchmeier,MichaelJ
中科院分区：
文献类型：
--
作者：
Saunders,AprilA;Ting,JoeyPC;Meisner,Jeffrey;Neuman,BenjaminW;Perez,Mar;delaTorre,JuanCarlos;Buchmeier,MichaelJ
淋巴细胞性脉络丛脑膜炎病毒表面糖蛋白前体的稳定信号肽（SSP）具有几个独特的特征。SSP是非常长的，在58个氨基酸，并包含两个疏水结构域，其序列是高度保守的旧和新世界沙粒病毒。为了更好地理解SSP的功能，通过体外诱变来靶向SSP内的高度保守元件，创建了一组点突变体和缺失突变体。我们也能够确认关键残基所需的单独的SSP功能的反式互补。使用这些方法，可以解析SSP的功能域。在表征我们的SSP突变体时，我们发现SSP参与病毒生命周期内的几种不同功能，超出病毒表面糖蛋白前体易位到内质网腔中。SSP是高效糖蛋白表达、SKI-1/S1 P蛋白酶对GP 1和GP 2的翻译后成熟切割、糖蛋白转运至细胞表面质膜、感染性病毒颗粒的形成以及酸性pH依赖性糖蛋白介导的细胞融合所必需的。
The stable signal peptide (SSP) of the lymphocytic choriomeningitis virus surface glycoprotein precursor has several unique characteristics. The SSP is unusually long, at 58 amino acids, and contains two hydrophobic domains, and its sequence is highly conserved among both Old and New World arenaviruses. To better understand the functions of the SSP, a panel of point and deletion mutants was created by in vitro mutagenesis to target the highly conserved elements within the SSP. We were also able to confirm critical residues required for separate SSP functions bytrans-complementation. Using these approaches, it was possible to resolve functional domains of the SSP. In characterizing our SSP mutants, we discovered that the SSP is involved in several distinct functions within the viral life cycle, beyond translocation of the viral surface glycoprotein precursor into the endoplasmic reticulum lumen. The SSP is required for efficient glycoprotein expression, posttranslational maturation cleavage of GP1 and GP2 by SKI-1/S1P protease, glycoprotein transport to the cell surface plasma membrane, formation of infectious virus particles, and acid pH-dependent glycoprotein-mediated cell fusion.