National Institutes of Health/National Human Genome Research Institute
P50GM082545
United States
Citation
Journal: Science / Year: 2019 Title: Structure of the Cdc48 segregase in the act of unfolding an authentic substrate. 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 / 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 ...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.
History
Deposition
Apr 22, 2019
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Header (metadata) release
May 8, 2019
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Map release
Jul 10, 2019
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Update
Aug 14, 2019
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Current status
Aug 14, 2019
Processing site: RCSB / Status: Released
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