ArticleNature communications2021
Structure and transport mechanism of P5B-ATPases.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Recent advances in understanding the regulatory mechanisms of P4-ATPase lipid flippases.Biochemical Society transactions · 2026Review
- Evolutionary Prevalence of the Electrostatic Switch Mechanism in P-type ATPases.The Journal of membrane biology · 2026Article
- ATP13A2 is involved in intracellular polyamine transport in lung epithelial cells.FEBS open bio · 2026Article
- ATP13A2-Mediated Spermine Export Modulates Lipid Catabolism in the Endolysosomal System of SH-SY5Y Cells.International journal of molecular sciences · 2026Article
- Structural insights into AQP3 channel closure upon pH and redox changes reveal an autoregulatory molecular mechanism.Nature communications · 2025Article
- Homology Modeling of Type-P5 ATPases from the Malaria Parasite: Insight into Their Functions and Evolution, and Implications About the Effect and Role of Intrinsically Disordered Protein Structure.Pathogens (Basel, Switzerland) · 2025Article
- Transition metal transporting P-type ATPases: terminal metal-binding domains serve as sensors for autoinhibitory tails.The FEBS journal · 2025Article
- Closed and open structures of the eukaryotic magnesium channel Mrs2 reveal the auto-ligand-gating regulation mechanism.Nature structural & molecular biology · 2025Article
- Lysosomal Ion Channels and Transporters: Recent Findings, Therapeutic Potential, and Technical Approaches.Bioelectricity · 2025Review
- 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
- Unveiling the hidden players: noncoding RNAs orchestrating polyamine metabolism in disease.Cell & bioscience · 2024Review
- Consensus, controversies, and conundrums of P4-ATPases: The emerging face of eukaryotic lipid flippases.The Journal of biological chemistry · 2024Review
- Diverse roles of the metal binding domains and transport mechanism of copper transporting P-type ATPases.Nature communications · 2024Article
- Metabolism of Polyamines and Kidney Disease: A Promising Therapeutic Target.Kidney diseases (Basel, Switzerland) · 2023Review
- ATP13A4 Upregulation Drives the Elevated Polyamine Transport System in the Breast Cancer Cell Line MCF7.Biomolecules · 2023Article
- Conformational cycle of human polyamine transporter ATP13A2.Nature communications · 2023Article
- Novel Green Fluorescent Polyamines to Analyze ATP13A2 and ATP13A3 Activity in the Mammalian Polyamine Transport System.Biomolecules · 2023Article
- ATP13A2 (PARK9) and basal ganglia function.Frontiers in neurology · 2023Review
- Yeast as a tool for membrane protein production and structure determination.FEMS yeast research · 2022Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In human cells, P5B-ATPases execute the active export of physiologically important polyamines such as spermine from lysosomes to the cytosol, a function linked to a palette of disorders. Yet, the overall shape of P5B-ATPases and the mechanisms of polyamine recognition, uptake and transport remain elusive. Here we describe a series of cryo-electron microscopy structures of a yeast homolog of human ATP13A2-5, Ypk9, determined at resolutions reaching 3.4 Å, and depicting three separate transport cycle intermediates, including spermine-bound conformations. Surprisingly, in the absence of cargo, Ypk9 rests in a phosphorylated conformation auto-inhibited by the N-terminus. Spermine uptake is accomplished through an electronegative cleft lined by transmembrane segments 2, 4 and 6. Despite the dramatically different nature of the transported cargo, these findings pinpoint shared principles of transport and regulation among the evolutionary related P4-, P5A- and P5B-ATPases. The data also provide a framework for analysis of associated maladies, such as Parkinson's disease.
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