Structure of the Cdc48 segregase in the act of unfolding an authentic substrate
Structure of the Cdc48 segregase in the act of unfolding an authentic substrate
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DOI：
10.1126/science.aax0486
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发表时间：
2019-08-02
期刊：
影响因子：
56.9
通讯作者：
Shen, Peter S.
中科院分区：
文献类型：
--
作者：
Cooney, Ian;Han, Han;Shen, Peter S.
细胞机器Cdc 48通过将其蛋白质底物从各种稳定环境（如细胞器或多亚基复合物）中分离而在多个生物途径中起作用。尽管进行了广泛的研究，Cdc 48的机制仍然不清楚，其结构与其他AAA+ ATP酶（腺苷三磷酸酶）的底物易位模型不一致。在这里，我们报告了一个3.7埃的分辨率结构的Cdc 48在复杂的衔接蛋白和一个本地基板。Cdc 48通过采用延伸穿过两个ATP酶环的中心孔的底物结合残基的螺旋构型来接合底物。这些发现表明Cdc 48和其他AAA+ ATP酶的蛋白质易位的统一的手-手机制。
The cellular machine Cdc48 functions in multiple biological pathways by segregating its protein substrates from a variety of stable environments such as organelles or multi-subunit complexes. Despite extensive studies, the mechanismof Cdc48 has remained obscure, and its reported structures are inconsistent with models of substrate translocation proposed for other AAA+ ATPases (adenosine triphosphatases). Here, we report a 3.7-angstrom-resolution structure of Cdc48 in complex with an adaptor protein and a native substrate. Cdc48 engages substrate by adopting a helical configuration of substrate-binding residues that extends through the central pore of both of the ATPase rings. These findings indicate a unified hand-over-hand mechanism of protein translocation by Cdc48 and other AAA+ ATPases.