Mothes W, Heinrich S U, Graf R, Nilsson I, von Heijne G, Brunner J, Rapoport T A
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell. 1997 May 16;89(4):523-33. doi: 10.1016/s0092-8674(00)80234-2.
As proteins are integrated into the membrane of the endoplasmic reticulum, some hydrophilic polypeptide segments are transported through the translocation channel, others remain in the cytosol, and hydrophobic transmembrane sequences are released into the lipid phase. We have addressed the molecular mechanism by which these events occur. We demonstrate that both the lumenal and the cytosolic domains of a membrane protein are synthesized while the ribosome is membrane bound, so that even cytosolic domains come in contact with the translocation channel. We also find that, before translation of the protein is terminated, transmembrane sequences can laterally exit the translocation channel and enter the lipid environment. These results have significant implications for the folding and assembly of membrane proteins.
当蛋白质整合到内质网膜中时，一些亲水性多肽片段通过转运通道运输，其他片段则保留在细胞质中，而疏水性跨膜序列则释放到脂质相中。我们已经研究了这些事件发生的分子机制。我们证明，膜蛋白的腔域和胞质域都是在核糖体与膜结合时合成的，这样即使是胞质域也会与转运通道接触。我们还发现，在蛋白质翻译终止之前，跨膜序列可以从转运通道横向退出并进入脂质环境。这些结果对膜蛋白的折叠和组装具有重要意义。
