6OAA

Cdc48-Npl4 complex processing poly-ubiquitinated substrate in the presence of ADP-BeFx, state 1

Summary for 6OAA

• Entry DOI: 10.2210/pdb6oaa/pdb
• EMDB information: 0665 0666 20000
• Descriptor: Cell division control protein 48, Nuclear protein localization protein 4, Ubiquitin, ... (5 entities in total)
• Functional Keywords: atpase, atpase complex, ubiquitin, quality control, motor protein
• Biological source: Saccharomyces cerevisiae S288C (Baker's yeast); More
• Total number of polymer chains: 6
• Total formula weight: 446672.14

Authors

Twomey, E.C.,Ji, Z.,Wales, T.E.,Bodnar, N.O.,Engen, J.R.,Rapoport, T.A. (deposition date: 2019-03-15, release date: 2019-07-03, Last modification date: 2024-03-20)

Primary citation

Twomey, E.C.,Ji, Z.,Wales, T.E.,Bodnar, N.O.,Ficarro, S.B.,Marto, J.A.,Engen, J.R.,Rapoport, T.A.
Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding.
Science, 365:-, 2019

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 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.

PubMed: 31249135
DOI: 10.1126/science.aax1033

Experimental method

ELECTRON MICROSCOPY (4.1 Å)