ArticleMolecular cell2021
Cryo-EM reveals mechanistic insights into lipid-facilitated polyamine export by human ATP13A2.
Article in Molecular cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Lysosomal dysfunction in neurodegenerative disease.Nature reviews. Neurology · 2026Review
- ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.Nature communications · 2026Article
- Progress in modelling ATP13A2-linked neurodegeneration.NPJ Parkinson's disease · 2026Review
- ATP13A2 is involved in intracellular polyamine transport in lung epithelial cells.FEBS open bio · 2026Article
- Pathophysiological Roles of Two Intracellular P-Type ATPases: The Cancer-Associated NaInternational journal of molecular sciences · 2026Review
- ATP13A2-Mediated Spermine Export Modulates Lipid Catabolism in the Endolysosomal System of SH-SY5Y Cells.International journal of molecular sciences · 2026Article
- Leucine Attenuates Osteoarthritis via mTORC1/LXRα-Mediated Macrophage Reprogramming and Rspo2/β-Catenin Axis Suppression.Cartilage · 2025Article
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- Structure and mechanism of human vesicular polyamine transporter.Nature communications · 2025Article
- Direct measurement of ATP13A2 polyamine-dependent ATPase activity following rapid purification of lysosomes.Methods in enzymology · 2025Article
- The structure and function of P5A-ATPases.Nature communications · 2024Article
- Polyamines mediate cellular energetics and lipid metabolism through mitochondrial respiration to facilitate virus replication.PLoS pathogens · 2024Article
- Nigral ATP13A2 depletion induces Parkinson's disease-related neurodegeneration in a pilot study in non-human primates.NPJ Parkinson's disease · 2024Article
- A novel ATP13A2 variant causing complicated hereditary spastic paraplegia.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024Article
- Lysosomal membrane transporter purification and reconstitution for functional studies.Molecular biology of the cell · 2024Article
- Activation and substrate specificity of the human P4-ATPase ATP8B1.Nature communications · 2023Article
- Structure and transport mechanism of the human calcium pump SPCA1.Cell research · 2023Article
- Structures and coordination chemistry of transporters involved in manganese and iron homeostasis.Biochemical Society transactions · 2023Review
- ATP13A4 Upregulation Drives the Elevated Polyamine Transport System in the Breast Cancer Cell Line MCF7.Biomolecules · 2023Article
- Parkinson's disease-associated ATP13A2/PARK9 functions as a lysosomal HNature communications · 2023Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The cytoplasmic polyamine maintains cellular homeostasis by chelating toxic metal cations, regulating transcriptional activity, and protecting DNA. ATP13A2 was identified as a lysosomal polyamine exporter responsible for polyamine release into the cytosol, and its dysfunction is associated with Alzheimer's disease and other neural degradation diseases. ATP13A2 belongs to the P5 subfamily of the P-type ATPase family, but its mechanisms remain unknown. Here, we report the cryoelectron microscopy (cryo-EM) structures of human ATP13A2 under four different conditions, revealing the structural coupling between the polyamine binding and the dephosphorylation. Polyamine is bound at the luminal tunnel and recognized through numerous electrostatic and π-cation interactions, explaining its broad specificity. The unique N-terminal domain is anchored to the lipid membrane to stabilize the E2P conformation, thereby accelerating the E1P-to-E2P transition. These findings reveal the distinct mechanism of P5B ATPases, thereby paving the way for neuroprotective therapy by activating ATP13A2.
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