ArticleNature structural & molecular biology2021
Targeted substrate loop insertion by VCP/p97 during PP1 complex disassembly.
Article in Nature structural & molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Molecular Tweezers Block the Functional Pore of a Protein Machine.Journal of the American Chemical Society · 2025Article
- Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway.Nature communications · 2024Article
- P-NADs:Heliyon · 2024Article
- SDS22 coordinates the assembly of holoenzymes from nascent protein phosphatase-1.Nature communications · 2024Article
- Cardiac-Specific Suppression of Valosin-Containing Protein Induces Progressive Heart Failure and Premature Mortality Correlating with Temporal Dysregulations in mTOR Complex 2 and Protein Phosphatase 1.International journal of molecular sciences · 2024Article
- Bidirectional substrate shuttling between the 26S proteasome and the Cdc48 ATPase promotes protein degradation.Molecular cell · 2024Article
- The p97/VCP adaptor UBXD1 drives AAA+ remodeling and ring opening through multi-domain tethered interactions.Nature structural & molecular biology · 2023Article
- Structural insights of the p97/VCP AAA+ ATPase: How adapter interactions coordinate diverse cellular functionality.The Journal of biological chemistry · 2023Review
- Structural basis of ubiquitin-independent PP1 complex disassembly by p97.The EMBO journal · 2023Article
- Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway.bioRxiv : the preprint server for biology · 2023Article
- Targeting of client proteins to the VCP/p97/Cdc48 unfolding machine.Frontiers in molecular biosciences · 2023Review
- The functional importance of VCP to maintaining cellular protein homeostasis.Biochemical Society transactions · 2022Review
- Multiple UBX proteins reduce the ubiquitin threshold of the mammalian p97-UFD1-NPL4 unfoldase.eLife · 2022Article
- Ubiquitin-directed AAA+ ATPase p97/VCP unfolds stable proteins crosslinked to DNA for proteolysis by SPRTN.The Journal of biological chemistry · 2022Article
- AAA+ proteins: one motor, multiple ways to work.Biochemical Society transactions · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The AAA-ATPase VCP/p97/Cdc48 unfolds proteins by threading them through its central pore, but how substrates are recognized and inserted into the pore in diverse pathways has remained controversial. Here, we show that p97, with its adapter p37, binds an internal recognition site (IRS) within inhibitor-3 (I3) and then threads a peptide loop into its channel to strip I3 off protein phosphatase-1 (PP1). Of note, the IRS is adjacent to the prime interaction site of I3 to PP1, and IRS mutations block I3 processing both in vitro and in cells. In contrast, amino- and carboxy-terminal regions of I3 are not required, and even circularization of I3 does not prevent I3 processing. This was confirmed by an in vitro Förster resonance energy transfer assay that allowed kinetic analysis of the reaction. Thus, our data uncover how PP1 is released from its inhibitory partner for activation and demonstrate a remarkable plasticity in substrate threading by p97.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.