Core protein of pestiviruses is processed at the C terminus by signal peptide peptidase
Core protein of pestiviruses is processed at the C terminus by signal peptide peptidase
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DOI：
10.1128/jvi.80.4.1915-1921.2006
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发表时间：
2006-02-01
影响因子：
5.4
通讯作者：
Rümenapf, T
中科院分区：
文献类型：
--
作者：
Heimann, M;Roman-Sosa, G;Rümenapf, T
瘟病毒的核心蛋白是通过病毒和细胞蛋白酶从多蛋白中释放出来的。在这里，我们报告了一个额外的膜内蛋白水解步骤，该步骤生成核心蛋白的 C 末端。猪瘟病毒 (CSFV) 核心蛋白的 C 末端加工被信号肽肽酶 (SPP) 特异性抑制剂 (Z-LL)(2)-酮阻断。通过显性失活 SPP D(265)A 突变体的过表达获得了相同的效果。 (Z-LL)(2)-酮的存在以浓度依赖性方式使CSFV的活力降低了近100倍。在使用诱导表达 SPP D(265)A 的细胞系的感染实验中也观察到病毒活力降低。 SPP 切割的位置通过对从病毒粒子纯化的核心蛋白进行 C 端测序来确定。 CSFV核心蛋白的C末端为丙氨酸(255)，位于信号肽的疏水中心。 CSFV核心蛋白C末端的膜内生成与丙型肝炎病毒核心蛋白的加工方案几乎相同。
The core protein of pestiviruses is released from the polyprotein by viral and cellular proteinases. Here we report on an additional intramembrane proteolytic step that generates the C terminus of the core protein. C-terminal processing of the core protein of classical swine fever virus (CSFV) was blocked by the inhibitor (Z-LL)(2)-ketone, which is specific for signal peptide peptidase (SPP). The same effect was obtained by overexpression of the dominant-negative SPP D(265)A mutant. The presence of (Z-LL)(2)-ketone reduced the viability of CSFV almost 100-fold in a concentration-dependent manner. Reduction of virus viability was also observed in infection experiments using a cell line that inducibly expressed SPP D(265)A. The position of SPP cleavage was determined by C-terminal sequencing of core protein purified from virions. The C terminus of CSFV core protein is alanine(255), and is located in the hydrophobic center of the signal peptide. The intramembrane generation of the C terminus of the CSFV core protein is almost identical to the processing scheme of the core protein of hepatitis C viruses.