Protein translocation across the ER membrane.
Protein translocation across the ER membrane.
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DOI：
10.1016/j.bbamem.2010.06.015
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发表时间：
2011-03
期刊：
影响因子：
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通讯作者：
R. Zimmermann;Susanne Eyrisch;Mazen Ahmad;V. Helms
中科院分区：
文献类型：
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作者：
R. Zimmermann;Susanne Eyrisch;Mazen Ahmad;V. Helms
蛋白质转运到内质网是真核细胞中大多数胞外蛋白质和许多可溶性细胞器蛋白质生物发生的第一步，也是决定性的一步。它在机制上与真细菌和古细菌的蛋白质输出以及新合成的膜蛋白整合到真细菌和古细菌的内质膜和质膜(尾锚膜蛋白除外)有关。通常，蛋白质转运到内质网涉及前体蛋白中的可切割氨基末端信号肽以及细胞质、内质膜和内质网腔中复杂的运输机械组件。根据前体蛋白的疏水性和/或总氨基酸含量，转运可以发生在共翻译或翻译后。各自的机制决定了对某些胞质运输成分的需求。这两种机制在内质网膜的水平上合并，特别是在膜中存在的异三聚体Sec61复合体上。Sec61复合体提供信号肽识别位点，形成多肽传导通道。显然，Sec61复合体受到多种配体的调控，如运输底物的信号肽、核糖体(共翻译运输)和内质网管腔分子伴侣Bip。BiP与进入的多肽结合有助于运输的效率和单向性。最近对Sec61复合体的结构以及酵母、人类寄生虫布鲁氏锥虫和哺乳动物的转运机制和机制的比较具有各种重要的机制和潜在的医学意义。这篇文章是题为蛋白质跨膜或插入膜的特刊的一部分。
Protein translocation into the endoplasmic reticulum (ER) is the first and decisive step in the biogenesis of most extracellular and many soluble organelle proteins in eukaryotic cells. It is mechanistically related to protein export from eubacteria and archaea and to the integration of newly synthesized membrane proteins into the ER membrane and the plasma membranes of eubacteria and archaea (with the exception of tail anchored membrane proteins). Typically, protein translocation into the ER involves cleavable amino terminal signal peptides in precursor proteins and sophisticated transport machinery components in the cytosol, the ER membrane, and the ER lumen. Depending on the hydrophobicity and/or overall amino acid content of the precursor protein, transport can occur co- or posttranslationally. The respective mechanism determines the requirements for certain cytosolic transport components. The two mechanisms merge at the level of the ER membrane, specifically, at the heterotrimeric Sec61 complex present in the membrane. The Sec61 complex provides a signal peptide recognition site and forms a polypeptide conducting channel. Apparently, the Sec61 complex is gated by various ligands, such as signal peptides of the transport substrates, ribosomes (in cotranslational transport), and the ER lumenal molecular chaperone, BiP. Binding of BiP to the incoming polypeptide contributes to efficiency and unidirectionality of transport. Recent insights into the structure of the Sec61 complex and the comparison of the transport mechanisms and machineries in the yeast Saccharomyces cerevisiae, the human parasite Trypanosoma brucei, and mammals have various important mechanistic as well as potential medical implications. This article is part of a Special Issue entitled Protein translocation across or insertion into membranes.