Structure of the Cdc48 segregase in the act of unfolding an authentic substrate.
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.
Mesh Terms:
Cryoelectron Microscopy, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Protein Domains, Saccharomyces cerevisiae Proteins, Substrate Specificity, Valosin Containing Protein
Cryoelectron Microscopy, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Protein Domains, Saccharomyces cerevisiae Proteins, Substrate Specificity, Valosin Containing Protein
Science
Date: Dec. 02, 2018
PubMed ID: 31249134
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