Eble B E, Lingappa V R, Ganem D
Department of Microbiology, University of California Medical Center, San Francisco 94143-0502.
J Virol. 1990 Mar;64(3):1414-9. doi: 10.1128/JVI.64.3.1414-1419.1990.
The coding region for the hepatitis B virus surface antigens contains three in-phase ATG codons which direct the synthesis of three related polypeptides. The 24-kilodalton major surface (or S) glycoprotein is initiated at the most distal ATG and is a transmembrane protein whose translocation across the bilayer is mediated by at least two uncleaved signal sequences. The product of the next upstream ATG is the 31-kilodalton pre-S2 protein, which contains 55 additional amino acids attached to the N terminus of the S protein. This pre-S2-specific domain is translocated into the endoplasmic reticulum. Using a coupled in vitro translation-translocation system, we showed that (i) the pre-S2 domain itself lacks functional signal sequence activity, (ii) its translocation across the endoplasmic reticulum membrane is mediated by downstream signals within the S domain, and (iii) the N-terminal signal sequence of the S protein can translocate upstream protein domains in the absence of other signals. The hepatitis B virus pre-S2 protein is an example of a natural protein which displays upstream domain translocation, a phenomenon whose existence was originally inferred from the behavior of synthetic fusion proteins in vitro.
乙肝病毒表面抗原的编码区包含三个同相位的ATG密码子，它们指导三种相关多肽的合成。24千道尔顿的主要表面（或S）糖蛋白由最末端的ATG起始，是一种跨膜蛋白，其跨双层膜的转运由至少两个未切割的信号序列介导。下一个上游ATG的产物是31千道尔顿的前S2蛋白，它在S蛋白的N末端含有55个额外的氨基酸。这个前S2特异性结构域被转运到内质网中。使用一个体外翻译-转运偶联系统，我们发现：（i）前S2结构域本身缺乏功能性信号序列活性；（ii）它跨内质网膜的转运由S结构域内的下游信号介导；（iii）在没有其他信号的情况下，S蛋白的N末端信号序列可以转运上游蛋白结构域。乙肝病毒前S2蛋白是一种天然蛋白的例子，它表现出上游结构域转运，这种现象最初是从体外合成融合蛋白的行为推断出来的。
