9YRC
p97Ufd1-Npl4 complex processing poly-ubiquitinated substrate in the presence of ATP
Summary for 9YRC
| Entry DOI | 10.2210/pdb9yrc/pdb |
| EMDB information | 73365 |
| Descriptor | Transitional endoplasmic reticulum ATPase, Nuclear protein localization protein 4 homolog, Ubiquitin recognition factor in ER-associated degradation protein 1, ... (6 entities in total) |
| Functional Keywords | p97, vcp, aaa+ atpase, translocase |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 9 |
| Total formula weight | 653269.12 |
| Authors | Li, H.,Rapoport, T. (deposition date: 2025-10-16, release date: 2026-03-25, Last modification date: 2026-04-29) |
| Primary citation | Li, H.,Guan, H.,Rapoport, T.A. The deubiquitinating enzyme Otu1 releases substrates from the conserved initiation complex of the Cdc48/p97 ATPase for proteasomal degradation. Sci Rep, 16:-, 2026 Cited by PubMed Abstract: Many eukaryotic proteins are modified with a polyubiquitin chain and then recruited to either the Cdc48 ATPase (p97 or VCP in mammals) or the 26S proteasome by conserved cofactors. They can then shuttle between the Cdc48 ATPase and the 26S proteasome before being degraded. How substrates avoid being trapped on the Cdc48 ATPase complex is incompletely understood, as they can undergo repeated cycles of translocation through the ATPase pore. Here, we show that the deubiquitinating enzyme (DUB) Otu1 (Yod1 in mammals) can break this futile cycle. Otu1 trims the ubiquitin chain of the substrate before its translocation through the Cdc48 pore is initiated, allowing transfer to the proteasome and subsequent degradation. A cryo-EM structure shows that the mammalian homolog Yod1 binds to p97 simultaneously with other Cdc48/p97 cofactors. As in the yeast system, polypeptide translocation through the ATPase pore is initiated by the unfolding of a ubiquitin molecule, suggesting that the mechanism of substrate processing is conserved in all eukaryotes. PubMed: 41795027DOI: 10.1038/s41598-026-42811-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.97 Å) |
Structure validation
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