National Institutes of Health/National Human Genome Research Institute
P50GM082545
米国
引用
ジャーナル: Science / 年: 2019 タイトル: Structure of the Cdc48 segregase in the act of unfolding an authentic substrate. 著者: 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 / 要旨: 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.