ArticleScientific reports2017
Deviation of the typical AAA substrate-threading pore prevents fatal protein degradation in yeast Cdc48.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway.Nature communications · 2024Article
- Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway.bioRxiv : the preprint server for biology · 2023Article
- Structural dynamics of AAA + ATPase Drg1 and mechanism of benzo-diazaborine inhibition.Nature communications · 2022Article
- Active conformation of the p97-p47 unfoldase complex.Nature communications · 2022Article
- Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase.Cell reports · 2022Article
- The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Proteostasis Factors.Journal of neuropathology and experimental neurology · 2021Review
- AAA+ ATPases in Protein Degradation: Structures, Functions and Mechanisms.Biomolecules · 2020Review
- Stairway to translocation: AAA+ motor structures reveal the mechanisms of ATP-dependent substrate translocation.Protein science : a publication of the Protein Society · 2020Review
- The Proteasome and Its Network: Engineering for Adaptability.Cold Spring Harbor perspectives in biology · 2020Review
- Substrate processing by the Cdc48 ATPase complex is initiated by ubiquitin unfolding.Science (New York, N.Y.) · 2019Article
- Structure of the Cdc48 segregase in the act of unfolding an authentic substrate.Science (New York, N.Y.) · 2019Article
- Cryo-EM structure of the essential ribosome assembly AAA-ATPase Rix7.Nature communications · 2019Article
- Article
- Biological and Pathological Implications of an Alternative ATP-Powered Proteasomal Assembly With Cdc48 and the 20S Peptidase.Frontiers in molecular biosciences · 2018Review
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded. By contrast, the aromatic residue in one of the two AAA rings of Cdc48 has been eliminated through evolution. Here, we show that artificial retrieval of this aromatic residue in Cdc48 is lethal, and essential features to support the threading mechanism are required to exhibit the lethal phenotype. In particular, genetic and biochemical analyses of the Cdc48 lethal mutant strongly suggested that when in complex with the 20S proteasome, essential proteins are abnormally forced to thread through the Cdc48 pore to become degraded, which was not detected in wild-type Cdc48. Thus, the widely applicable threading model is less effective for wild-type Cdc48; rather, Cdc48 might function predominantly through an as-yet-undetermined mechanism.
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