Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins
Topological changes in the transmembrane domains of hepatitis C virus envelope glycoproteins
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DOI：
10.1093/emboj/cdf295
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发表时间：
2002-06-17
期刊：
影响因子：
11.4
通讯作者：
Dubuisson, J
中科院分区：
文献类型：
--
作者：
Cocquerel, L;de Beeck, AO;Dubuisson, J
丙型肝炎病毒蛋白是一种由信号肽酶和病毒蛋白酶裂解而成的多蛋白。丙型肝炎病毒包膜蛋白E1和E2跨膜结构域C端内部信号序列的行为对下游多肽的拓扑结构至关重要。我们通过标记E1和E2表位并分析它们在选择性渗透细胞中的可及性，确定了信号序列切割前后这些跨膜结构域的拓扑结构。我们发现，在内质网的信号肽酶裂解后，这些跨膜结构域的c端取向从管腔变为细胞质。这些跨膜结构域的动态行为是独特的，它与它们的多功能性有关。通过将E1和E2的c端指向胞质并成为跨膜结构域的一部分，E1和E2的c端信号序列有助于实现新的功能：(1)膜锚定；（ii） E1E2异二聚化；（三）内质网保留。
Hepatitis C virus proteins are synthesized as a polyprotein cleaved by a signal peptidase and viral proteases. The behaviour of internal signal sequences at the C-terminus of the transmembrane domains of hepatitis C virus envelope proteins E1 and E2 is essential for the topology of downstream polypeptides. We determined the topology of these transmembrane domains before and after signal sequence cleavage by tagging E1 and E2 with epitopes and by analysing their accessibility in selectively permeabilized cells. We showed that, after cleavage by signal peptidase in the endoplasmic reticulum, the C-terminal orientation of these transmembrane domains changed from luminal to cytosolic. The dynamic behaviour of these transmembrane domains is unique and it is linked to their multifunctionality. By reorienting their C-terminus toward the cytosol and being part of a transmembrane domain, the signal sequences at the C-terminus of E1 and E2 contribute to new functions: (i) membrane anchoring; (ii) E1E2 heterodimerization; and (iii) endoplasmic reticulum retention.