Chuck S L, Yao Z, Blackhart B D, McCarthy B J, Lingappa V R
Department of Medicine, University of California 94143.
Nature. 1990 Jul 26;346(6282):382-5. doi: 10.1038/346382a0.
Apolipoprotein B (apo B) is crucial for the transport of cholesterol in humans. It is a large secretory protein that mediates the uptake of low-density lipoproteins and renders several forms of lipid droplets soluble in the blood. The binding of lipid by apo B also prevents this hydrophobic protein from precipitating in aqueous solution. In the endoplasmic reticulum, nascent secretory proteins must be translocated through an aqueous channel in the membrane into the aqueous lumen, so some novel form of processing may be necessary to maintain the solubility of apo B during its translocation. We have discovered that the biogenesis of apo B in cell-free systems does indeed involve a new variation on protein translocation: unlike typical secretory proteins, apo B is synthesized as a series of transmembrane chains with large cytoplasmic domains and progressively longer amino-terminal regions that are protected against added proteases during the translocation process. In contrast to typical transmembrane proteins, these transmembrane chains are not integrated into the bilayer. Moreover, the transmembrane chains with the shortest protected domains are precursors of forms whose protection is progressively extended to cover the length of the protein. This stepwise conversion occurs post-translationally for the most part. We propose a model on the basis of these findings for the biogenesis of apo B.
载脂蛋白B（apo B）对人体胆固醇的运输至关重要。它是一种大型分泌蛋白，介导低密度脂蛋白的摄取，并使多种形式的脂滴在血液中可溶。apo B与脂质的结合还可防止这种疏水蛋白在水溶液中沉淀。在内质网中，新生的分泌蛋白必须通过膜中的水相通道转运到水相腔中，因此可能需要某种新的加工形式来在apo B转运过程中维持其溶解性。我们发现，无细胞系统中apo B的生物合成确实涉及蛋白质转运的一种新变体：与典型的分泌蛋白不同，apo B作为一系列具有大细胞质结构域和逐渐变长的氨基末端区域的跨膜链合成，这些区域在转运过程中受到保护，免受添加的蛋白酶的作用。与典型的跨膜蛋白相反，这些跨膜链并未整合到双层膜中。此外，具有最短保护结构域的跨膜链是其保护作用逐渐扩展以覆盖整个蛋白质长度的形式的前体。这种逐步转化在很大程度上发生在翻译后。基于这些发现，我们提出了一个apo B生物合成的模型。
