2019年8月2日，哈佛医学院的Tom A. Rapoport研究组在《科学》发表论文，报道了Cdc48 ATP酶复合物处理底物是从去折叠泛素起始的。

研究人员报道了Cdc48 ATP酶与Ufd1/Npl4和多聚物化底物形成的复合物冷冻电镜结构。结构表明，Cdc48复合物通过去折叠泛素分子开启底物处理程序。展开的泛素分子与Npl4结合，并通过两个六聚ATP酶环投射其N端片段。第二个环的孔洞形成阶梯，从而作为传送带将多肽通过中心孔移动。通过引发泛素的展开，Cdc48 ATP酶复合物可以处理多种底物。

据了解，Cdc48腺苷三磷酸酶(ATP酶，在哺乳动物中叫做p97或VCP)及其辅因子Ufd1/Npl4从膜或大分子复合物中提取多泛素化的蛋白，进行后续的蛋白酶体降解。Cdc48如何处理这些不同的、而且经常是折叠好的底物尚不清楚。

附：英文原文

Title: Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding

Author: Edward C. Twomey, Zhejian Ji, Thomas E. Wales, Nicholas O. Bodnar, Scott B. Ficarro, Jarrod A. Marto, John R. Engen, Tom A. Rapoport

Issue&Volume: Vol 365 Issue 6452

Abstract: The Cdc48 adenosine triphosphatase (ATPase) (p97 or valosin-containing protein in mammals) and its cofactor Ufd1/Npl4 extract polyubiquitinated proteins from membranes or macromolecular complexes for subsequent degradation by the proteasome. How Cdc48 processes its diverse and often well-folded substrates is unclear. Here, we report cryo–electron microscopy structures of the Cdc48 ATPase in complex with Ufd1/Npl4 and polyubiquitinated substrate. The structures show that the Cdc48 complex initiates substrate processing by unfolding a ubiquitin molecule. The unfolded ubiquitin molecule binds to Npl4 and projects its N-terminal segment through both hexameric ATPase rings. Pore loops of the second ring form a staircase that acts as a conveyer belt to move the polypeptide through the central pore. Inducing the unfolding of ubiquitin allows the Cdc48 ATPase complex to process a broad range of substrates.

DOI: 10.1126/science.aax1033

Source: https://science.sciencemag.org/content/365/6452/eaax1033