ArticleCell discovery2022
Cryo-EM structures of human p97 double hexamer capture potentiated ATPase-competent state.
Article in Cell discovery, 2022. 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, 25 citations in OpenAlex.
- Development and Structural Characterization of UTE-156, a Covalent Inhibitor of the VCP/p97 AAA+ ATPase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Cryo-EM structural analyses reveal plant-specific adaptations of the CDC48 unfoldase.Plant communications · 2026Article
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- Molecular Basis of VCPIP1 and P97/VCP Interaction Reveals Its Functions in Post-Mitotic Golgi Reassembly.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors.Communications chemistry · 2024Article
- Article
- Allosteric activation of VCP, an AAA unfoldase, by small molecule mimicry.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- TheeLife · 2024Article
- Analysis of the Conformational Landscape of the N-Domains of the AAA ATPase p97: Disentangling the Continuous Conformational Variability in Partially Symmetrical Complexes.International journal of molecular sciences · 2024Article
- Characterizing ATP processing by the AAA+ protein p97 at the atomic level.Nature chemistry · 2024Article
- Valosin-Containing Protein (VCP)/p97 Oligomerization.Sub-cellular biochemistry · 2024Review
- Molecular Mechanisms Driving and Regulating the AAA+ ATPase VCP/p97, an Important Therapeutic Target for Treating Cancer, Neurological and Infectious Diseases.Biomolecules · 2023Review
- Article
- The functional importance of VCP to maintaining cellular protein homeostasis.Biochemical Society transactions · 2022Review
- Communication network within the essential AAA-ATPase Rix7 drives ribosome assembly.PNAS nexus · 2022Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The conserved ATPase p97 (Cdc48 in yeast) and adaptors mediate diverse cellular processes through unfolding polyubiquitinated proteins and extracting them from macromolecular assemblies and membranes for disaggregation and degradation. The tandem ATPase domains (D1 and D2) of the p97/Cdc48 hexamer form stacked rings. p97/Cdc48 can unfold substrates by threading them through the central pore. The pore loops critical for substrate unfolding are, however, not well-ordered in substrate-free p97/Cdc48 conformations. How p97/Cdc48 organizes its pore loops for substrate engagement is unclear. Here we show that p97/Cdc48 can form double hexamers (DH) connected through the D2 ring. Cryo-EM structures of p97 DH reveal an ATPase-competent conformation with ordered pore loops. The C-terminal extension (CTE) links neighboring D2s in each hexamer and expands the central pore of the D2 ring. Mutations of Cdc48 CTE abolish substrate unfolding. We propose that the p97/Cdc48 DH captures a potentiated state poised for substrate engagement.
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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.