The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation.
The ribosome-bound quality control complex remains associated to aberrant peptides during their proteasomal targeting and interacts with Tom1 to limit protein aggregation.
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DOI：
10.1091/mbc.e16-10-0746
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发表时间：
2017-05-01
影响因子：
3.3
通讯作者：
Fromont-Racine M
中科院分区：
文献类型：
--
作者：
Defenouillère Q;Namane A;Mouaikel J;Jacquier A;Fromont-Racine M
参与蛋白质质量控制机制的RQC复合物在将异常肽护送到蛋白酶体期间也作为核糖体未结合的复合物存在。E3泛素连接酶Tom 1是新鉴定的RQC复合物的这种轻版本的伙伴，并且是预防聚集所需的。蛋白质质量控制机制消除有缺陷的多肽，以确保蛋白质稳定并避免蛋白质聚集体的毒性。在真核生物中，核糖体结合的质量控制（RQC）复合物检测异常的新生肽，这些肽由于翻译终止功能障碍而停滞在60 S核糖体颗粒中。RQC复合物使异常多肽聚泛素化，并招募Cdc 48六聚体从60 S颗粒中提取它们，以将它们护送到蛋白酶体进行降解。尽管已经描述了从停滞的60 S识别到RQC复合物的异常肽聚泛素化的步骤，但导致这些缺陷翻译产物的蛋白酶体降解的机制仍然未知。我们在这里表明，RQC复合物也存在作为一个核糖体未结合的复合物在护送异常肽的蛋白酶体。此外，我们确定了一个新的合作伙伴，这种轻版本的RQC复合物，E3泛素连接酶Tom 1。Tom 1与异常新生肽相互作用，并且在不存在Rqc 1的情况下限制其积累和聚集是必不可少的;然而，其E3泛素连接酶活性不是必需的。总之，这些结果揭示了Tom 1在蛋白质质量控制，聚集预防，因此，蛋白质稳态维护中的新作用。
The RQC complex involved in protein quality control mechanisms also exists as a ribosome-unbound complex during the escort of aberrant peptides to the proteasome. The E3 ubiquitin ligase Tom1 is a newly identified partner of this light version of the RQC complex and is required for aggregate prevention. Protein quality control mechanisms eliminate defective polypeptides to ensure proteostasis and to avoid the toxicity of protein aggregates. In eukaryotes, the ribosome-bound quality control (RQC) complex detects aberrant nascent peptides that remain stalled in 60S ribosomal particles due to a dysfunction in translation termination. The RQC complex polyubiquitylates aberrant polypeptides and recruits a Cdc48 hexamer to extract them from 60S particles in order to escort them to the proteasome for degradation. Whereas the steps from stalled 60S recognition to aberrant peptide polyubiquitylation by the RQC complex have been described, the mechanism leading to proteasomal degradation of these defective translation products remains unknown. We show here that the RQC complex also exists as a ribosome-unbound complex during the escort of aberrant peptides to the proteasome. In addition, we identify a new partner of this light version of the RQC complex, the E3 ubiquitin ligase Tom1. Tom1 interacts with aberrant nascent peptides and is essential to limit their accumulation and aggregation in the absence of Rqc1; however, its E3 ubiquitin ligase activity is not required. Taken together, these results reveal new roles for Tom1 in protein quality control, aggregate prevention, and, therefore, proteostasis maintenance.