Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Trends Cell Biol. 2021 Jun;31(6):473-484. doi: 10.1016/j.tcb.2021.01.002. Epub 2021 Jan 30.
Membranes surrounding cells or organelles represent barriers to proteins and other molecules. However, specific proteins can cross membranes by different translocation systems, the best studied being the Sec61/SecY channel. This channel forms a hydrophilic, hourglass-shaped membrane channel, with a lateral gate towards the surrounding lipid. However, recent studies show that an aqueous pore is not required in other cases of protein translocation. The Hrd1 complex, mediating the retrotranslocation of misfolded proteins from the endoplasmic reticulum (ER) lumen into the cytosol, contains multispanning proteins with aqueous luminal and cytosolic cavities, and lateral gates juxtaposed in a thinned membrane region. A locally thinned, distorted lipid bilayer also allows protein translocation in other systems, suggesting a new paradigm to overcome the membrane barrier.
细胞膜或细胞器膜是蛋白质和其他分子的屏障。然而，特定的蛋白质可以通过不同的转位系统穿过膜，其中研究得最好的是 Sec61/SecY 通道。该通道形成亲水的沙漏形膜通道，其侧向门朝向周围的脂质。然而，最近的研究表明，在其他蛋白质转位的情况下，并不需要水相孔道。Hrd1 复合物介导内质网腔中错误折叠的蛋白质从内质网腔返回到细胞质中的逆向转位，该复合物包含具有水相腔和细胞质腔以及侧向门的多跨膜蛋白，侧向门并置在膜变薄的区域。局部变薄、扭曲的脂双层也允许其他系统中的蛋白质转运，这表明一种克服膜屏障的新范例。
