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

• DOI: 10.1126/science.aax0486
• Publication Date: 2019-06-27T23:15:11Z
• Authors: 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
• Keywords: 0301 basic medicine; 03 medical and health sciences; Saccharomyces cerevisiae Proteins; Protein Domains; Valosin Containing Protein; Cryoelectron Microscopy; Intracellular Signaling Peptides and Proteins; Immunoprecipitation; Substrate Specificity

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 has remained obscure, and reported structures are inconsistent with models substrate translocation proposed for other AAA+ ATPases (adenosine triphosphatases). Here, we report 3.7-angstrom-resolution structure complex an adaptor native substrate. engages adopting helical configuration substrate-binding residues that extends through central pore both ATPase rings. These findings indicate unified hand-over-hand ATPases.