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-Structure paper
Title | Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding. |
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Journal, issue, pages | Science, Vol. 365, Issue 6452, Year 2019 |
Publish date | Aug 2, 2019 |
Authors | Edward C Twomey / Zhejian Ji / Thomas E Wales / Nicholas O Bodnar / Scott B Ficarro / Jarrod A Marto / John R Engen / Tom A Rapoport / |
PubMed Abstract | The Cdc48 adenosine triphosphatase (ATPase) (p97 or valosin-containing protein in mammals) and its cofactor Ufd1/Npl4 extract polyubiquitinated proteins from membranes or macromolecular complexes for ...The Cdc48 adenosine triphosphatase (ATPase) (p97 or valosin-containing protein in mammals) and its cofactor Ufd1/Npl4 extract polyubiquitinated proteins from membranes or macromolecular complexes for subsequent degradation by the proteasome. How Cdc48 processes its diverse and often well-folded substrates is unclear. Here, we report cryo-electron microscopy structures of the Cdc48 ATPase in complex with Ufd1/Npl4 and polyubiquitinated substrate. The structures show that the Cdc48 complex initiates substrate processing by unfolding a ubiquitin molecule. The unfolded ubiquitin molecule binds to Npl4 and projects its N-terminal segment through both hexameric ATPase rings. Pore loops of the second ring form a staircase that acts as a conveyer belt to move the polypeptide through the central pore. Inducing the unfolding of ubiquitin allows the Cdc48 ATPase complex to process a broad range of substrates. |
External links | Science / PubMed:31249135 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.6 - 4.1 Å |
Structure data | EMDB-0665: Cdc48-Ufd1/Npl4 complex processing poly-ubiquitinated substrate in the presence of ATP EMDB-0666: Cdc48-Ufd1/Npl4 complex processing poly-ubiquitinated substrate in the presence of ADP-BeFx, state 1 EMDB-20000: Cdc48-Ufd1/Npl4 complex processing poly-ubiquitinated substrate in the presence of ADP-BeFx, state 2 |
Chemicals | ChemComp-ATP: ChemComp-ADP: ChemComp-ZN: ChemComp-BEF: |
Source |
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Keywords | MOTOR PROTEIN / ATPase / ATPase complex / ubiquitin / quality control |