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单体酵母和哺乳动物质体 Sec61 复合物与翻译核糖体相互作用的结构。

Structure of monomeric yeast and mammalian Sec61 complexes interacting with the translating ribosome.

机构信息

Gene Center Munich and Center for Integrated Protein Science, Department of Chemistry and Biochemistry, Ludwig-Maximilians-Universität München, Feodor-Lynen-Strasse 25, 81377 Munich, Germany.

出版信息

Science. 2009 Dec 4;326(5958):1369-73. doi: 10.1126/science.1178535. Epub 2009 Oct 29.

DOI:10.1126/science.1178535
PMID:19933108
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2920595/
Abstract

The trimeric Sec61/SecY complex is a protein-conducting channel (PCC) for secretory and membrane proteins. Although Sec complexes can form oligomers, it has been suggested that a single copy may serve as an active PCC. We determined subnanometer-resolution cryo-electron microscopy structures of eukaryotic ribosome-Sec61 complexes. In combination with biochemical data, we found that in both idle and active states, the Sec complex is not oligomeric and interacts mainly via two cytoplasmic loops with the universal ribosomal adaptor site. In the active state, the ribosomal tunnel and a central pore of the monomeric PCC were occupied by the nascent chain, contacting loop 6 of the Sec complex. This provides a structural basis for the activity of a solitary Sec complex in cotranslational protein translocation.

摘要

三聚体 Sec61/SecY 复合物是一种用于分泌蛋白和膜蛋白的蛋白传导通道 (PCC)。尽管 Sec 复合物可以形成寡聚体,但有人提出单个拷贝可能作为活性 PCC。我们确定了真核核糖体-Sec61 复合物的亚纳米分辨率冷冻电子显微镜结构。结合生化数据,我们发现,在空闲和活跃状态下,Sec 复合物不是寡聚体,主要通过两个细胞质环与通用核糖体衔接子位点相互作用。在活跃状态下,核糖体隧道和单体 PCC 的中央孔被新生链占据,与 Sec 复合物的环 6 接触。这为翻译共转移中单个 Sec 复合物的活性提供了结构基础。

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本文引用的文献

1
Translocation of proteins through the Sec61 and SecYEG channels.蛋白质通过Sec61和SecYEG通道的易位。
Curr Opin Cell Biol. 2009 Aug;21(4):501-7. doi: 10.1016/j.ceb.2009.04.010. Epub 2009 May 18.
2
The lateral gate of SecYEG opens during protein translocation.在蛋白质转运过程中,SecYEG的外侧门打开。
J Biol Chem. 2009 Jun 5;284(23):15805-14. doi: 10.1074/jbc.M901855200. Epub 2009 Apr 14.
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Conformational transition of Sec machinery inferred from bacterial SecYE structures.从细菌SecYE结构推断出的Sec转运体的构象转变
Nature. 2008 Oct 16;455(7215):988-91. doi: 10.1038/nature07421.
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Structure of a complex of the ATPase SecA and the protein-translocation channel.ATP酶SecA与蛋白质转运通道复合物的结构
Nature. 2008 Oct 16;455(7215):936-43. doi: 10.1038/nature07335.
5
A single Sec61-complex functions as a protein-conducting channel.单个Sec61复合物作为蛋白质传导通道发挥作用。
Biochim Biophys Acta. 2008 Dec;1783(12):2375-83. doi: 10.1016/j.bbamcr.2008.08.005. Epub 2008 Aug 20.
6
Single copies of Sec61 and TRAP associate with a nontranslating mammalian ribosome.Sec61和TRAP的单拷贝与非翻译状态的哺乳动物核糖体相关联。
Structure. 2008 Jul;16(7):1126-37. doi: 10.1016/j.str.2008.05.003.
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Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics.使用分子动力学将原子结构灵活拟合到电子显微镜图谱中。
Structure. 2008 May;16(5):673-83. doi: 10.1016/j.str.2008.03.005.
8
Ribosome binding of a single copy of the SecY complex: implications for protein translocation.SecY复合体单拷贝的核糖体结合:对蛋白质转运的影响。
Mol Cell. 2007 Dec 28;28(6):1083-92. doi: 10.1016/j.molcel.2007.10.034.
9
Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes.蛋白质跨真核生物内质网和细菌质膜的转运
Nature. 2007 Nov 29;450(7170):663-9. doi: 10.1038/nature06384.
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Protein translocation is mediated by oligomers of the SecY complex with one SecY copy forming the channel.蛋白质转运由SecY复合体的寡聚体介导,其中一个SecY拷贝形成通道。
Cell. 2007 Apr 6;129(1):97-110. doi: 10.1016/j.cell.2007.02.036.