The transmembrane domains of hepatitis C virus envelope glycoproteins E1 and E2 play a major role in heterodimerization
The transmembrane domains of hepatitis C virus envelope glycoproteins E1 and E2 play a major role in heterodimerization
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DOI：
10.1074/jbc.m003003200
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发表时间：
2000-10-06
影响因子：
4.8
通讯作者：
Dubuisson, J
中科院分区：
文献类型：
--
作者：
De Beeck, AO;Montserret, R;Dubuisson, J
病毒包膜蛋白的寡聚化对控制病毒的组装和融合至关重要。丙型肝炎病毒包膜糖蛋白El和E2的跨膜结构域（TMDs）在E1E2异源二聚体的生物发生过程中发挥了多种功能。这使得它们在已知的跨膜序列中非常独特。在这篇报道中，我们使用丙氨酸扫描插入诱变技术在El和E2的tmd中检测它们在E1E2异源二聚体组装中的作用。在El或E2的TMD中心或El的TMD的n端插入丙氨酸可显著减少异源二聚化，表明这些结构域在丙型肝炎病毒包膜糖蛋白的组装中发挥重要作用。为了更好地理解含有GXXXG基序的El TMD的丙氨酸扫描数据，我们通过圆二色性和核磁共振分析了El TMD n端序列参与异源二聚化的E1-(350-370)肽的三维结构。丙氨酸扫描结果和我们获得的三维分子模型为在分子水平上理解丙型肝炎病毒包膜糖蛋白异二聚化机制提供了第一个框架。
Oligomerization of viral envelope proteins is essential to control virus assembly and fusion. The transmembrane domains (TMDs) of hepatitis C virus envelope glycoproteins El and E2 have been shown to play multiple functions during the biogenesis of E1E2 heterodimer. This makes them very unique among known transmembrane sequences. In this report, we used alanine scanning insertion mutagenesis in the TMDs of El and E2 to examine their role in the assembly of E1E2 heterodimer. Alanine insertion within the center of the TMDs of El or E2 or in the N-terminal part of the TMD of El dramatically reduced heterodimerization, demonstrating the essential role played by these domains in the assembly of hepatitis C virus envelope glycoproteins. To better understand the alanine scanning data obtained for the TMD of El which contains GXXXG motifs, we analyzed by circular dichroism and nuclear magnetic resonance the three dimensional structure of the E1-(350-370) peptide encompassing the N-terminal sequence of the TMD of El involved in heterodimerization. Alanine scanning results and the three-dimensional molecular model we obtained provide the first framework for a molecular level understanding of the mechanism of hepatitis C virus envelope glycoprotein heterodimerization.