Proteomics

Dataset Information

0

Translocation of polyubiquitinated protein substrates by the hexameric Cdc48 ATPase


ABSTRACT: The hexameric Cdc48 ATPase (p97 or VCP in mammals) cooperates with its cofactor Ufd1/Npl4 to extract polyubiquitinated proteins from membranes or macromolecular complexes for degradation by the proteasome. Here, we clarify how the Cdc48 complex unfolds its substrates and translocates polypeptides with branchpoints. The Cdc48 complex recognizes primarily polyubiquitin chains, rather than the attached substrate. Cdc48 and Ufd1/Npl4 cooperatively bind the polyubiquitin chain, resulting in the unfolding of one ubiquitin molecule (initiator). Next, the ATPase pulls on the initiator ubiquitin and moves all ubiquitin molecules linked to its C-terminus through the central pore of the hexameric double-ring, causing transient ubiquitin unfolding. When the ATPase reaches the isopeptide bond of the substrate, it can translocate and unfold both N- and C-terminal segments. Ubiquitins linked to the branchpoint of the initiator dissociate from Ufd1/Npl4 and move outside the central pore, resulting in the release of unfolded, polyubiquitinated substrate from Cdc48.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: John R. Engen  

LAB HEAD: John R. Engen

PROVIDER: PXD027639 | Pride | 2022-01-19

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
020621_Cdc48_complex_Und1_IA_final_peptide.csv Csv
170521_Cdc48_Und1_IA_final_peptide.csv Csv
1_Cdc48complex_ADP_10m.raw.zip Raw
1_Cdc48complex_ADP_10s.raw.zip Raw
1_Cdc48complex_ADP_1m.raw.zip Raw
Items per page:
1 - 5 of 37
altmetric image

Publications

Translocation of polyubiquitinated protein substrates by the hexameric Cdc48 ATPase.

Ji Zhejian Z   Li Hao H   Peterle Daniele D   Paulo Joao A JA   Ficarro Scott B SB   Wales Thomas E TE   Marto Jarrod A JA   Gygi Steven P SP   Engen John R JR   Rapoport Tom A TA  

Molecular cell 20211223 3


The hexameric Cdc48 ATPase (p97 or VCP in mammals) cooperates with its cofactor Ufd1/Npl4 to extract polyubiquitinated proteins from membranes or macromolecular complexes for degradation by the proteasome. Here, we clarify how the Cdc48 complex unfolds its substrates and translocates polypeptides with branchpoints. The Cdc48 complex recognizes primarily polyubiquitin chains rather than the attached substrate. Cdc48 and Ufd1/Npl4 cooperatively bind the polyubiquitin chain, resulting in the unfold  ...[more]

Similar Datasets

2024-02-23 | PXD042878 | Pride
2019-09-13 | PXD013001 | Pride
2015-10-30 | PXD002972 | Pride
2024-03-14 | PXD043563 | Pride
2024-03-14 | PXD043565 | Pride
2021-08-26 | PXD024479 | Pride
2021-09-22 | PXD025209 | Pride
2021-09-22 | PXD025928 | Pride
2022-10-12 | PXD036076 | Pride
2020-03-18 | PXD017538 | Pride