Dissecting the molecular organization of the translocon-associated protein complex.
Dissecting the molecular organization of the translocon-associated protein complex.
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DOI：
10.1038/ncomms14516
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发表时间：
2017-02-20
影响因子：
16.6
通讯作者：
Förster F
中科院分区：
文献类型：
--
作者：
Pfeffer S;Dudek J;Schaffer M;Ng BG;Albert S;Plitzko JM;Baumeister W;Zimmermann R;Freeze HH;Engel BD;Förster F
在真核细胞中，三分之一的蛋白质必须通过内质网（ER）蛋白质转运体转运穿过内质网膜或插入内质网膜。转运体相关蛋白（TRAP）复合物是转运体的一个组成部分，它以依赖底物的方式调节信号序列和跨膜螺旋的插入，从而协助Sec61蛋白质传导通道。在此，我们利用冷冻电子断层扫描（CET）来研究进化上不同的生物中天然转运体的结构以及来自人类患者的与疾病相关的TRAP突变纤维母细胞。通过亚断层图像分析检测到的结构差异为剖析TRAP复合物的分子组织奠定了基础。我们确定了复合物中四个TRAP亚基的位置，为了解它们各自的功能提供了见解。所揭示的一个核心转运体组分的分子结构增进了我们对膜蛋白生物发生的理解，并阐明了TRAP在人类先天性糖基化障碍中的作用。
转运体相关蛋白复合物（TRAP）是内质网蛋白质转运体的一个关键组分。在此，作者研究来自人类疾病患者和藻类细胞的天然转运体结构，以确定TRAP复合物的分子组织。
In eukaryotic cells, one-third of all proteins must be transported across or inserted into the endoplasmic reticulum (ER) membrane by the ER protein translocon. The translocon-associated protein (TRAP) complex is an integral component of the translocon, assisting the Sec61 protein-conducting channel by regulating signal sequence and transmembrane helix insertion in a substrate-dependent manner. Here we use cryo-electron tomography (CET) to study the structure of the native translocon in evolutionarily divergent organisms and disease-linked TRAP mutant fibroblasts from human patients. The structural differences detected by subtomogram analysis form a basis for dissecting the molecular organization of the TRAP complex. We assign positions to the four TRAP subunits within the complex, providing insights into their individual functions. The revealed molecular architecture of a central translocon component advances our understanding of membrane protein biogenesis and sheds light on the role of TRAP in human congenital disorders of glycosylation. The translocon-associated protein complex (TRAP) is a crucial component of the endoplasmic reticulum protein translocon. Here the authors study native translocon structures from human disease patients and algae cells to determine the molecular organization of the TRAP complex.