PXD027639

PXD027639 is an original dataset announced via ProteomeXchange.

Title	Translocation of polyubiquitinated protein substrates by the hexameric Cdc48 ATPase
Description	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.
HostingRepository	PRIDE
AnnounceDate	2022-01-25
AnnouncementXML	Submission_2022-01-25_09:38:19.395.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John R. Engen
SpeciesList	scientific name: Saccharomyces cerevisiae (Baker's yeast); NCBI TaxID: 4932;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2021-07-29 02:01:03	ID requested
⏵ 1	2022-01-25 09:38:20	announced

Ji Z, Li H, Peterle D, Paulo JA, Ficarro SB, Wales TE, Marto JA, Gygi SP, Engen JR, Rapoport TA, Translocation of polyubiquitinated protein substrates by the hexameric Cdc48 ATPase. Mol Cell, 82(3):570-584.e8(2022) [pubmed]

submitter keyword: AAA ATPase, translocation, ubiquitin, p97, VCP, Npl4, Ufd1, unfolding, HDX-MS, hydrogen deuterium exchange mass spectrometry

John R. Engen
contact affiliation	Department of Chemistry & Chemical Biology, Northeastern University
contact email	j.engen@northeastern.edu
lab head
John R. Engen
contact affiliation	Northeastern University
contact email	j.engen@northeastern.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD027639
     1. Label: PRIDE project
     2. Name: Translocation of polyubiquitinated protein substrates by the hexameric Cdc48 ATPase