DC2 and KCP2 mediate the interaction between the oligosaccharyltransferase and the ER translocon.
DC2 and KCP2 mediate the interaction between the oligosaccharyltransferase and the ER translocon.
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DOI：
10.1083/jcb.201702159
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发表时间：
2017-11-06
期刊：
影响因子：
--
通讯作者：
Gilmore R
中科院分区：
文献类型：
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作者：
Shrimal S;Cherepanova NA;Gilmore R
寡糖基转移酶的STT3A异构体与蛋白质转运通道相邻，以催化内质网中蛋白质的共翻译N -糖基化。Shrimal等人表明，寡糖基转移酶的STT3A异构体的DC2和KCP2亚基负责介导STT3A复合物与蛋白质转运通道之间的相互作用，从而使蛋白质能够进行共翻译N -糖基化。
在后生动物中，寡糖基转移酶的STT3A异构体位于蛋白质转运通道附近，以催化内质网中蛋白质的共翻译N -连接糖基化。STT3A复合物与转运通道之间相互作用的机制尚未得到解决。我们利用缺乏DC2或KCP2蛋白的基因改造人类细胞，发现DC2的缺失会导致蛋白质共翻译N -糖基化出现缺陷，这种缺陷类似于STT3A - / - 表型。生化分析表明，DC2和KCP2负责介导蛋白质转运通道与STT3A复合物之间的相互作用。重要的是，缺乏DC2和KCP2的STT3A复合物是稳定的且具有酶活性。缺失突变显示，DC2的C末端尾部的一个保守基序对于组装到STT3A复合物中至关重要，而腔内环和N末端细胞质区段对于STT3A和Sec61复合物之间的功能性相互作用是必需的。
The STT3A isoform of the oligosaccharyltransferase is adjacent to the protein translocation channel to catalyze co-translational N-glycosylation of proteins in the endoplasmic reticulum. Shrimal et al. show that the DC2 and KCP2 subunits of the STT3A isoform of the oligosaccharyltransferase are responsible for mediating the interaction between the STT3A complex and the protein translocation channel to allow co-translational N-glycosylation of proteins. In metazoan organisms, the STT3A isoform of the oligosaccharyltransferase is localized adjacent to the protein translocation channel to catalyze co-translational N-linked glycosylation of proteins in the endoplasmic reticulum. The mechanism responsible for the interaction between the STT3A complex and the translocation channel has not been addressed. Using genetically modified human cells that are deficient in DC2 or KCP2 proteins, we show that loss of DC2 causes a defect in co-translational N-glycosylation of proteins that mimics an STT3A−/− phenotype. Biochemical analysis showed that DC2 and KCP2 are responsible for mediating the interaction between the protein translocation channel and the STT3A complex. Importantly, DC2- and KCP2-deficient STT3A complexes are stable and enzymatically active. Deletion mutagenesis revealed that a conserved motif in the C-terminal tail of DC2 is critical for assembly into the STT3A complex, whereas the lumenal loop and the N-terminal cytoplasmic segment are necessary for the functional interaction between the STT3A and Sec61 complexes.
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Sec61和陷阱的单副本与非翻译哺乳动物核糖体相关。
影响因子：
5.7
作者：
Menetret, Jean-Francois;Hegde, Ramanujan S.;Aguiar, Mike;Gygi, Steven P.;Park, Eunyong;Rapoport, Tom A.;Akey, Christopher W.
通讯作者：
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影响因子：
16.6
作者：
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通讯作者：
Förster F
影响因子：
1.9
作者：
Ghosh, Arunabha;Urquhart, Jill;Clayton-Smith, Jill
通讯作者：
Clayton-Smith, Jill
影响因子：
16.6
作者：
Pfeffer S;Dudek J;Schaffer M;Ng BG;Albert S;Plitzko JM;Baumeister W;Zimmermann R;Freeze HH;Engel BD;Förster F
通讯作者：
Förster F
影响因子：
46.9
作者：
通讯作者：
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