POSTTRANSLATIONAL ALTERATIONS IN TRANSMEMBRANE TOPOLOGY OF THE HEPATITIS-B VIRUS LARGE ENVELOPE PROTEIN
POSTTRANSLATIONAL ALTERATIONS IN TRANSMEMBRANE TOPOLOGY OF THE HEPATITIS-B VIRUS LARGE ENVELOPE PROTEIN
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DOI：
10.1002/j.1460-2075.1994.tb06509.x
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发表时间：
1994-05-15
期刊：
影响因子：
11.4
通讯作者：
GERLICH, WH
中科院分区：
文献类型：
--
作者：
BRUSS, V;LU, XY;GERLICH, WH
位于B型肝炎病毒大包膜蛋白（LHB）N-末端的preS结构域参与（i）病毒核衣壳的形成和（ii）与宿主细胞的结合。虽然第一个功能表明在病毒体组装过程中preS结构域的胞质位置，但作为附着位点的功能需要其穿过脂质双层的易位并最终暴露在病毒体表面上。我们比较了新合成的LHB在内质网（ER）膜上的跨膜拓扑结构与其在分泌病毒体包膜上的拓扑结构。蛋白酶的敏感性和糖基化的情况下，新合成的LHB的整个preS域仍然在ER囊泡的胞质侧。然而，从转染的细胞培养物中分泌的或从持久性病毒携带者的血液中分离的病毒粒子在大约一半的LHB分子中暴露其表面上的抗体结合位点和preS结构域的蛋白水解切割位点。因此，preS结构域似乎通过一种新的翻译后易位机制被转运穿过病毒脂质屏障，以实现病毒体组装和附着于宿主细胞的双重功能。
The preS domain at the N-terminus of the large envelope protein (LHBs) of the hepatitis B virus is involved in (i) envelopment of viral nucleocapsids and (ii) binding to the host cell. While the first function suggests a cytosolic location of the preS domain during virion assembly, the function as an attachment site requires its translocation across the lipid bilayer and final exposure on the virion surface. We compared the transmembrane topology of newly synthesized LHBs in the endoplasmic reticulum (ER) membrane with its topology in the envelope of secreted virions. Protease sensitivity and the absence of glycosylation suggest that the entire preS domain of newly synthesized LHBs remains at the cytosolic side of ER vesicles. However, virions secreted from transfected cell cultures or isolated from the blood of persistent virus carriers expose antibody binding sites and proteolytic cleavage sites of the preS domain at their surface in approximately half of the LHBs molecules. Thus, preS domains appear to be transported across the viral lipid barrier by a novel post-translational translocation mechanism to fulfil a dual function in virion assembly and attachment to the host cell.