Haßdenteufel Sarah, Klein Marie-Christine, Melnyk Armin, Zimmermann Richard
Medical Biochemistry & Molecular Biology, Saarland University, Building 44, Kirrbergerstr, D-66421 Homburg, Germany.
Biochem Cell Biol. 2014 Dec;92(6):499-509. doi: 10.1139/bcb-2014-0043. Epub 2014 May 27.
Protein transport into the human endoplasmic reticulum (ER) is relevant to the biogenesis of most soluble and membrane proteins of organelles, which are involved in endo- or exo-cytsosis. It involves amino-terminal signal peptides in the precursor polypeptides and various transport components in the cytosol plus the ER, and can occur co- or post-translationally. The two mechanisms merge at the level of the ER membrane, specifically at the level of the heterotrimeric Sec61 complex, which forms a dynamic polypeptide-conducting channel in the ER membrane. Since the mammalian ER is also the main intracellular calcium storage organelle, and the Sec61 complex is calcium permeable, the Sec61 complex is tightly regulated in its equilibrium between the closed and open conformations, or "gated", by ligands, such as signal peptides of the transport substrates and the ER lumenal Hsp70-type molecular chaperone BiP. Furthermore, BiP binding to the incoming polypeptide contributes to the efficiency and unidirectionality of transport. Recent insights into the structure and dynamic equilibrium of the Sec61 complex have various mechanistic as well as medical implications.
蛋白质转运到人类内质网（ER）与大多数细胞器可溶性和膜蛋白的生物合成相关，这些蛋白参与胞吞或胞吐作用。它涉及前体多肽中的氨基末端信号肽以及细胞质和内质网中的各种转运成分，并且可以在翻译过程中或翻译后发生。这两种机制在内质网膜水平上合并，特别是在异源三聚体Sec61复合物水平上，该复合物在内质网膜中形成一个动态的多肽传导通道。由于哺乳动物内质网也是主要的细胞内钙储存细胞器，并且Sec61复合物具有钙通透性，因此Sec61复合物在其关闭和开放构象之间的平衡（即“门控”）受到配体的严格调控，这些配体包括转运底物的信号肽和内质网腔Hsp70型分子伴侣BiP。此外，BiP与进入的多肽结合有助于提高转运效率和单向性。最近对Sec61复合物结构和动态平衡的深入了解具有多种机制和医学意义。
