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Science. 2019 Jun 27. pii: eaax0486. doi: 10.1126/science.aax0486. [Epub ahead of print]

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

Author information

1
Department of Biochemistry, 15 N. Medical Drive East, University of Utah, Salt Lake City, UT 84112, USA.
2
Department of Chemistry and Biochemistry, C100 BNSN, Brigham Young University, Provo, UT 84602, USA.
3
Department of Biochemistry, 15 N. Medical Drive East, University of Utah, Salt Lake City, UT 84112, USA. chris@biochem.utah.edu peter.shen@biochem.utah.edu.

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. Here, we report a 3.7 Å 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.

PMID:
31249134
DOI:
10.1126/science.aax0486

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