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

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 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.

SUBMITTER: Cooney I

PROVIDER: S-EPMC7362759 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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

Cooney Ian I Han Han H Stewart Michael G MG Carson Richard H RH Hansen Daniel T DT Iwasa Janet H JH Price John C JC Hill Christopher P CP Shen Peter S PS

Science (New York, N.Y.) 20190627 6452

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 pro ...[more]

PMID: 31249134

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Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding.

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