The transmembrane domain of hepatitis C virus glycoprotein E1 is a signal for static retention in the endoplasmic reticulum
The transmembrane domain of hepatitis C virus glycoprotein E1 is a signal for static retention in the endoplasmic reticulum
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DOI：
10.1128/jvi.73.4.2641-2649.1999
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发表时间：
1999-04-01
影响因子：
5.4
通讯作者：
Dubuisson, J
中科院分区：
文献类型：
--
作者：
Cocquerel, L;Duvet, S;Dubuisson, J
丙型肝炎病毒（HCV）糖蛋白E1和E2聚集形成非共价异二聚体，在细胞内积聚在内质网（ER）中。与观察到的具有KDEL或KKXX ER靶向信号的蛋白质相反，HCV糖蛋白复合物的内质网定位是由于静态保留在该室中，而不是从顺式高尔基区提取。当E2在没有E1的情况下表达或含有CD4外畴与E2跨膜结构域（TMD）融合的嵌合蛋白表达时，也观察到内质网中的静态保留。虽然他们不排除E1中存在细胞内定位信号，但这些数据确实表明E2的TMD是HCV糖蛋白复合物的内质网保留信号。在本研究中，含有CD4或CD8外畴的嵌合蛋白融合到E1的c端疏水序列中，被证明在内质网中定位，这表明E1的TMD也是内质网定位的信号。此外，这些嵌合蛋白没有被高尔基酶加工，这表明E1的TMD负责在内质网中真正保留，而不是通过高尔基体再循环。总之，这些数据表明至少有两个信号（E1和E2的tmd）参与了HCV糖蛋白复合物的内质网保留。
Hepatitis C virus (HCV) glycoproteins E1 and E2 assemble to form a noncovalent heterodimer which, in the cell, accumulates in the endoplasmic reticulum (ER), Contrary to what is observed for proteins with a KDEL or a KKXX ER-targeting signal, the ER localization of the HCV glycoprotein complex is due to a static retention in this compartment rather than to its retrieval from the cis-Golgi region. A static retention in the ER is also observed when E2 is expressed in the absence of E1 or for a chimeric protein containing the ectodomain of CD4 in fusion with the transmembrane domain (TMD) of E2. Although they do not exclude the presence of an intracellular localization signal in E1, these data do suggest that the TMD of E2 is an ER retention signal for HCV glycoprotein complex. In this study chimeric proteins containing the ectodomain of CD4 or CD8 fused to the C-terminal hydrophobic sequence olf E1 were shown to be localized in the ER, indicating that the TMD of E1 is also a signal for ER localization. In addition, these chimeric proteins were not processed by Golgi enzymes, indicating that the TMD of E1 is responsible for true retention in the ER, without recycling through the Golgi apparatus. Together, these data suggest that at least two signals (TMDs of E1 and E2) are involved in ER retention of the HCV glycoprotein complex.