Barthelme Dominik, Sauer Robert T
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Max Planck Institute for Infection Biology, Berlin 10117, Germany.
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
J Mol Biol. 2016 May 8;428(9 Pt B):1861-9. doi: 10.1016/j.jmb.2015.11.015. Epub 2015 Dec 1.
The AAA+ Cdc48 ATPase (alias p97 or VCP) is a key player in multiple ubiquitin-dependent cell signaling, degradation, and quality control pathways. Central to these broad biological functions is the ability of Cdc48 to interact with a large number of adaptor proteins and to remodel macromolecular proteins and their complexes. Different models have been proposed to explain how Cdc48 might couple ATP hydrolysis to forcible unfolding, dissociation, or remodeling of cellular clients. In this review, we provide an overview of possible mechanisms for substrate unfolding/remodeling by this conserved and essential AAA+ protein machine and their adaption and possible biological function throughout evolution.
AAA+ 型 Cdc48 三磷酸腺苷酶(别名 p97 或 VCP)是多种泛素依赖性细胞信号传导、降解及质量控制途径中的关键因子。Cdc48 能够与大量衔接蛋白相互作用,并重塑大分子蛋白质及其复合物,这对于这些广泛的生物学功能至关重要。人们提出了不同模型来解释 Cdc48 如何将 ATP 水解与细胞底物的强制解折叠、解离或重塑相耦合。在本综述中,我们概述了这种保守且必需的 AAA+ 蛋白机器使底物解折叠/重塑的可能机制,以及它们在整个进化过程中的适应性和可能的生物学功能。