Antiribophorin antibodies inhibit the targeting to the ER membrane of ribosomes containing nascent secretory polypeptides.
Antiribophorin antibodies inhibit the targeting to the ER membrane of ribosomes containing nascent secretory polypeptides.
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抗蛋白酶抗体抑制含有新生分泌多肽的核糖体的ER膜的靶向。
DOI：
10.1083/jcb.111.4.1335
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发表时间：
1990-10
影响因子：
7.8
通讯作者：
Kreibich, G
中科院分区：
文献类型：
--
作者：
Yu, Y H;Sabatini, D D;Kreibich, G
针对核糖体结合蛋白I和II（粗糙内质网特有的两种膜糖蛋白）的多克隆抗体，可抑制分泌蛋白生长激素在狗胰腺或大鼠肝脏微粒体腔中的共翻译转运。正如所预期的，针对核糖体结合蛋白I胞质结构域内表位的位点特异性抗体能够有效抑制转运，而针对该蛋白腔结构域内表位的抗体则无效。由于单价Fab片段与完整的IgG分子具有相同的抑制作用，核糖体结合蛋白必定与转运位点紧密相关，因此很可能在转运过程的某个阶段发挥作用。在所有情况下，抑制转运的抗体也会导致总蛋白质合成显著减少，并且中和其抑制转运能力的处理也会阻止其对蛋白质合成的抑制作用。如果抗体阻断了由信号识别颗粒（SRP）诱导的多肽延伸停滞的膜介导缓解作用，就会出现这种情况。抗体只有在转运开始前加入才有效。在这种情况下，它们会阻止含有mRNA和新生链的活性核糖体靶向内质网膜。因此，核糖体结合蛋白要么直接参与靶向过程，要么与靶向位点非常接近，以至于抗体在空间上阻断了转运过程的早期阶段。
Polyclonal antibodies directed against ribophorins I and II, two membrane glycoproteins characteristic of the rough endoplasmic reticulum, inhibit the cotranslational translocation of a secretory protein growth hormone into the lumen of dog pancreas or rat liver microsomes. As expected, site-specific antibodies to epitopes located within the cytoplasmic domain of ribophorin I, but not antibodies to epitopes in the luminal domain of this protein, were effective in inhibiting translocation. Since monovalent Fab fragments were as inhibitory as intact IgG molecules, ribophorins must be closely associated with the translocation site and, therefore, are likely to function at some stage in the translocation process. In all cases, the antibodies that inhibited translocation also caused a significant reduction in total protein synthesis and treatments that neutralized their capacity to inhibit translocation also prevented their inhibitory effect on protein synthesis. This would be expected if the antibodies blocked the membrane-mediated relief of the SRP-induced arrest of polypeptide elongation. The antibodies were effective only when added before translocation was allowed to begin. In this case, they prevented the targeting of active ribosomes containing mRNA and nascent chains to the ER membrane. Thus, ribophorins must either directly participate in targeting or be so close to the targeting site that the antibodies sterically blocked this early phase of the translocation process.