The Tat system proofreads FeS protein substrates and directly initiates the disposal of rejected molecules
The Tat system proofreads FeS protein substrates and directly initiates the disposal of rejected molecules
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DOI：
10.1038/emboj.2008.132
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发表时间：
2008-08-06
期刊：
影响因子：
11.4
通讯作者：
Di Cola, Alessandra
中科院分区：
文献类型：
--
作者：
Matos, Cristina F. R. O.;Robinson, Colin;Di Cola, Alessandra
双精氨酸转位(TAT)系统通过细菌质膜运输折叠蛋白，包括在细胞质中接收辅因子的FeS蛋白。我们研究了两种大肠杆菌TAT底物，NRFC和NapG，以检查该系统如何或是否只输出正确折叠和组装的FES蛋白。有了NRFC，即使是预测的四个FES中心中的一个替换也完全阻止了出口，这表明校对活动有效。FES突变体迅速降解，但只有当它们与TAT转运子相互作用时；它们在TAT缺失菌株中稳定，在野生型细胞中同样稳定，如果信号肽双精氨酸基序被移除以阻断靶向。NAPG得到了基本类似的结果。因此，TAT设备校对这些底物，并直接启动废弃分子的周转。突变的FeS底物的周转完全依赖于TATA/E亚基，TATA/E亚基被认为参与了转位的后期阶段，我们认为部分易位在FES蛋白的综合质量控制系统中触发底物周转。
The twin-arginine translocation (Tat) system transports folded proteins across the bacterial plasma membrane, including FeS proteins that receive their cofactors in the cytoplasm. We have studied two Escherichia coli Tat substrates, NrfC and NapG, to examine how, or whether, the system exports only correctly folded and assembled FeS proteins. With NrfC, substitutions in even one of four predicted FeS centres completely block export, indicating an effective proofreading activity. The FeS mutants are rapidly degraded but only if they interact with the Tat translocon; they are stable in a tat deletion strain and equally stable in wild-type cells if the signal peptide twin-arginine motif is removed to block targeting. Basically similar results are obtained with NapG. The Tat apparatus thus proofreads these substrates and directly initiates the turnover of rejected molecules. Turnover of mutated FeS substrates is completely dependent on the TatA/E subunits that are believed to be involved in the late stages of translocation, and we propose that partial translocation triggers substrate turnover within an integrated quality control system for FeS proteins.