ArticleThe Journal of biological chemistry2014
PA1b inhibitor binding to subunits c and e of the vacuolar ATPase reveals its insecticidal mechanism.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Agrochemical innovation for crop health: moving forward through dynamic disorder.Frontiers in plant science · 2025Article
- Article
- Heterologous production of the insecticidal pea seed albumin PA1 protein by Pichia pastoris and protein engineering to potentiate aphicidal activity via fusion to snowdrop lectin Galanthus nivalis agglutinin; GNA).Microbial cell factories · 2023Article
- Residues of Legume AG41 Peptide Crucial to Its Bio-Insecticidal Activity.Biomolecules · 2023Article
- Restoration of Cathepsin D Level via L-Serine Attenuates PPA-Induced Lysosomal Dysfunction in Neuronal Cells.International journal of molecular sciences · 2022Article
- The Plant V-ATPase.Frontiers in plant science · 2022Review
- Eruca sativa seed napin structural insights and thorough functional characterization.Scientific reports · 2021Article
- Molecular basis of V-ATPase inhibition by bafilomycin A1.Nature communications · 2021Article
- Anopheles metabolic proteins in malaria transmission, prevention and control: a review.Parasites & vectors · 2020Review
- Bafilomycin C1 induces G0/G1 cell-cycle arrest and mitochondrial-mediated apoptosis in human hepatocellular cancer SMMC7721 cells.The Journal of antibiotics · 2018Article
- Approaches to altering particle distributions in cryo-electron microscopy sample preparation.Acta crystallographica. Section D, Structural biology · 2018Review
- The interaction of the bioinsecticide PA1b (Pea Albumin 1 subunit b) with the insect V-ATPase triggers apoptosis.Scientific reports · 2017Article
- The potential use of single-particle electron microscopy as a tool for structure-based inhibitor design.Acta crystallographica. Section D, Structural biology · 2017Article
- Molecular basis for the binding and modulation of V-ATPase by a bacterial effector protein.PLoS pathogens · 2017Article
- Rotating with the brakes on and other unresolved features of the vacuolar ATPase.Biochemical Society transactions · 2016Review
- An introduction to sample preparation and imaging by cryo-electron microscopy for structural biology.Methods (San Diego, Calif.) · 2016Article
- Recent Insights into the Structure, Regulation, and Function of the V-ATPases.Trends in biochemical sciences · 2015Review
- Structure of the vacuolar H+-ATPase rotary motor reveals new mechanistic insights.Structure (London, England : 1993) · 2015Article
- The use of SMALPs as a novel membrane protein scaffold for structure study by negative stain electron microscopy.Biochimica et biophysica acta · 2015Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
The vacuolar ATPase (V-ATPase) is a 1MDa transmembrane proton pump that operates via a rotary mechanism fuelled by ATP. Essential for eukaryotic cell homeostasis, it plays central roles in bone remodeling and tumor invasiveness, making it a key therapeutic target. Its importance in arthropod physiology also makes it a promising pesticide target. The major challenge in designing lead compounds against the V-ATPase is its ubiquitous nature, such that any therapeutic must be capable of targeting particular isoforms. Here, we have characterized the binding site on the V-ATPase of pea albumin 1b (PA1b), a small cystine knot protein that shows exquisitely selective inhibition of insect V-ATPases. Electron microscopy shows that PA1b binding occurs across a range of equivalent sites on the c ring of the membrane domain. In the presence of Mg·ATP, PA1b localizes to a single site, distant from subunit a, which is predicted to be the interface for other inhibitors. Photoaffinity labeling studies show radiolabeling of subunits c and e. In addition, weevil resistance to PA1b is correlated with bafilomycin resistance, caused by mutation of subunit c. The data indicate a binding site to which both subunits c and e contribute and inhibition that involves locking the c ring rotor to a static subunit e and not subunit a. This has implications for understanding the V-ATPase mechanism and that of inhibitors with therapeutic or pesticidal potential. It also provides the first evidence for the position of subunit e within the complex.
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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.