An Update on Sec61 Channel Functions, Mechanisms, and Related Diseases.
An Update on Sec61 Channel Functions, Mechanisms, and Related Diseases.
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DOI：
10.3389/fphys.2017.00887
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发表时间：
2017
影响因子：
4
通讯作者：
Zimmermann R
中科院分区：
文献类型：
--
作者：
Lang S;Pfeffer S;Lee PH;Cavalié A;Helms V;Förster F;Zimmermann R
人类有核细胞的内质网(ER)膜上含有蛋白转运子，它促进了几乎所有新合成的多肽与胞内和胞外途径细胞器的膜整合或转位。转运子由多肽传导的Sec61通道和其他几个与异三聚体Sec61复合体永久或暂时相关的蛋白质和复合体组成。这一蛋白质集合促进了前体多肽的内质网靶向，通过Sec61复合体运输的前体多肽的修饰，以及Sec61通道门控，即动态调节成孔亚基以调节前体运输和钙外流。最近，来自人类细胞系或患者成纤维细胞，甚至是完整细胞的天然内质网膜泡中的转运蛋白的冷冻电子断层扫描提供了对天然转位蛋白和Sec61通道的结构和动力学的前所未有的深入了解。这些结构数据根据不同的Sec61通道活动，包括核糖体受体功能、膜插入和新合成多肽的转位，以及Sec61通道作为被动内质网钙泄漏通道的可能生理作用进行了讨论。此外，对Sec61经络的结构洞察被纳入到Sec61经络相关疾病的概述和最新进展中--Sec61经络病--及其治疗的新治疗概念。
The membrane of the endoplasmic reticulum (ER) of nucleated human cells harbors the protein translocon, which facilitates membrane integration or translocation of almost every newly synthesized polypeptide targeted to organelles of the endo- and exocytotic pathway. The translocon comprises the polypeptide-conducting Sec61 channel and several additional proteins and complexes that are permanently or transiently associated with the heterotrimeric Sec61 complex. This ensemble of proteins facilitates ER targeting of precursor polypeptides, modification of precursor polypeptides in transit through the Sec61 complex, and Sec61 channel gating, i.e., dynamic regulation of the pore forming subunit to mediate precursor transport and calcium efflux. Recently, cryoelectron tomography of translocons in native ER membrane vesicles, derived from human cell lines or patient fibroblasts, and even intact cells has given unprecedented insights into the architecture and dynamics of the native translocon and the Sec61 channel. These structural data are discussed in light of different Sec61 channel activities including ribosome receptor function, membrane insertion, and translocation of newly synthesized polypeptides as well as the putative physiological roles of the Sec61 channel as a passive ER calcium leak channel. Furthermore, the structural insights into the Sec61 channel are incorporated into an overview and update on Sec61 channel-related diseases—the Sec61 channelopathies—and novel therapeutic concepts for their treatment.
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霉菌酮通过选择性地阻断SEC61转运，从而颠覆了免疫力。
DOI：
10.1084/jem.20160662
发表时间：
2016-12-12
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Baron L;Paatero AO;Morel JD;Impens F;Guenin-Macé L;Saint-Auret S;Blanchard N;Dillmann R;Niang F;Pellegrini S;Taunton J;Paavilainen VO;Demangel C
通讯作者：
Demangel C
影响因子：
64.5
作者：
Ast, Tslil;Cohen, Galit;Schuldiner, Maya
通讯作者：
Schuldiner, Maya
影响因子：
15.9
作者：
Besse, Whitney;Dong, Ke;Somlo, Stefan
通讯作者：
Somlo, Stefan
影响因子：
64.8
作者：
Besemer, J;Harant, H;Lindley, IJD
通讯作者：
Lindley, IJD
影响因子：
3.4
作者：
Bano-Polo, Manuel;Martinez-Garay, Carlos A.;Mingarro, Ismael
通讯作者：
Mingarro, Ismael