A new type of intracellular retention signal identified in a pestivirus structural glycoprotein
A new type of intracellular retention signal identified in a pestivirus structural glycoprotein
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DOI：
10.1096/fj.12-207191
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发表时间：
2012-08-01
期刊：
影响因子：
4.8
通讯作者：
Meyers, Gregor
中科院分区：
文献类型：
--
作者：
Burrack, Sandra;Aberle, Daniel;Meyers, Gregor
将膜蛋白分选到细胞内细胞器中对于细胞功能至关重要。病毒利用细胞内运输和滞留系统将包膜蛋白浓缩在病毒出芽的位点。瘟病毒是一组与人类丙型肝炎病毒密切相关的猪和反刍动物的重要病原体，由病毒RNA翻译的E-rns蛋白由感染细胞分泌并存在于感染动物的血清中。蛋白质的分泌被认为是其作为与其RNA酶活性相关的病毒毒力因子的功能的关键。然而，近似95%的E-rns分子保留在感染的细胞内。不同Erns片段与CD 72的C末端的融合允许在病毒蛋白的C末端65 aa内鉴定保留信号。该C末端序列代表其膜锚并折叠成平面内结合至膜表面的两亲性螺旋。残基L183、I190和L208对于E-rns的细胞内定位是重要的。在CD 8 α融合蛋白中，滞留信号呈现在细胞质上而不是ER膜的腔面上仍然导致滞留。因此，E-rns在其C-末端两亲性螺旋中含有在膜的两面上都有活性的细胞内保留信号。Burrack，S.，Aberle，D.，Burck，J.，Ulrich，A.美国，Meyers，G.在瘟病毒结构糖蛋白中发现的一种新型胞内滞留信号。FASEB J.26，3292-3305（2012）。www.fasebj.org
Sorting of membrane proteins into intracellular organelles is crucial for cell function. Viruses exploit intracellular transport and retention systems to concentrate envelope proteins at the site of virus budding. In pestiviruses, a group of important pathogens of pigs and ruminants closely related to human hepatitis C virus, the E-rns protein translated from the viral RNA is secreted from the infected cells and found in the serum of infected animals. Secretion of the protein is regarded as crucial for its function as a viral virulence factor associated with its RNase activity. However, similar to 95% of the E-rns molecules are retained within the infected cell. Fusion of different Erns fragments to the C terminus of CD72 allowed identification of a retention signal within the C-terminal 65 aa of the viral protein. This C-terminal sequence represents its membrane anchor and folds into an amphipathic helix binding in-plane to the membrane surface. Residues L183, I190, and L208 are important for intracellular location of E-rns. Presentation of the retention signal on the cytoplasmic instead of the luminal face of the ER membrane in CD8 alpha fusion proteins still led to retention. Thus, E-rns contains in its C-terminal amphipathic helix an intracellular retention signal that is active on both faces of the membrane.-Burrack, S., Aberle, D., Burck, J., Ulrich, A. S., Meyers, G. A new type of intracellular retention signal identified in a pestivirus structural glycoprotein. FASEB J. 26, 3292-3305 (2012). www.fasebj.org