A conserved island of BAG6/Scythe is related to ubiquitin domains and participates in short hydrophobicity recognition
A conserved island of BAG6/Scythe is related to ubiquitin domains and participates in short hydrophobicity recognition
复制标题
DOI：
10.1111/febs.13618
复制
发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Hirofumi Tanaka;Toshiki Takahashi;Yiming Xie;R. Minami;Y. Yanagi;Mizuki Hayashishita;R. Suzuki;Naoto Yokota;M. Shimada;T. Mizushima;N. Kuwabara;R. Kato;H. Kawahara
中科院分区：
文献类型：
--
作者：
Hirofumi Tanaka;Toshiki Takahashi;Yiming Xie;R. Minami;Y. Yanagi;Mizuki Hayashishita;R. Suzuki;Naoto Yokota;M. Shimada;T. Mizushima;N. Kuwabara;R. Kato;H. Kawahara
BAG6（也称为 Scythe）与新合成蛋白质的暴露疏水区域相互作用，并通过仍有待阐明的机制护送它们进入降解机器。在这项研究中，我们提供了证据表明 BAG6 与模型缺陷蛋白底物 CL1 的物理相互作用方式直接取决于其短疏水性。我们发现 BAG6 的 N 末端包含一个进化上保守的岛，暂定为 BAG6 泛素连接结构域。 BAG6 N 端片段中该结构域的部分删除会导致多聚泛素化多肽的细胞识别以及细胞内和体外疏水性介导的 CL1 降解决定子的识别失效。这些观察结果表明，BAG6 泛素连接结构域提供了一个平台，用于区分具有较短疏水性延伸的底物作为缺陷蛋白质的信号。
BAG6 (also called Scythe) interacts with the exposed hydrophobic regions of newly synthesized proteins and escorts them to the degradation machinery through mechanisms that remain to be elucidated. In this study, we provide evidence that BAG6 physically interacts with the model defective protein substrate CL1 in a manner that depends directly on its short hydrophobicity. We found that the N terminus of BAG6 contains an evolutionarily conserved island tentatively designated the BAG6 ubiquitin‐linked domain. Partial deletion of this domain in the BAG6 N‐terminal fragment abolished in cell recognition of polyubiquitinated polypeptides as well as the hydrophobicity‐mediated recognition of the CL1 degron in cell and in vitro. These observations suggest a mechanism whereby the BAG6 ubiquitin‐linked domain provides a platform for discriminating substrates with shorter hydrophobicity stretches as a signal for defective proteins.