美国犹他州大学Peter S. Shen和Christopher P. Hill研究组合作解析了Cdc48在去折叠底物蛋白时的冷冻电镜结构。该研究于2019年8月2日发表于国际学术期刊《科学》上。

研究人员报道了Cdc48与一个接头蛋白以及一个未变性底物形成的复合物结构，分辨率达到了3.7埃。Cdc48通过采用底物结合残基的螺旋结构与底物结合，这种螺旋结构可穿过两个ATP酶环型结构中间的孔洞。这些发现表明，Cdc48与其他AAA+ ATP酶一样通过一个统一的手拉手（hand-over-hand）机制对蛋白进行易位。

据了解，细胞机器Cdc48通过将其蛋白底物从各种稳定的环境中（例如细胞器和多亚基复合物等）分离出来，在多种生物途径中发挥功能。尽管进行了大量的研究，但Cdc48的工作机制仍然不清楚，并且其已报道的结构与根据其他AAA+ ATP酶（腺苷三磷酸酶）所提出的底物易位模型不一致。

附：英文原文

Title: Structure of the Cdc48 segregase in the act of unfolding an authentic substrate

Author: Ian Cooney, Han Han, Michael G. Stewart, Richard H. Carson, Daniel T. Hansen, Janet H. Iwasa, John C. Price, Christopher P. Hill, Peter S. Shen

Issue&Volume: Vol 365 Issue 6452

Abstract: 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 mechanism of 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.

DOI: 10.1126/science.aax0486

Source:https://science.sciencemag.org/content/365/6452/502