ArticleThe Journal of biological chemistry2010
The rapid-onset dystonia parkinsonism mutation D923N of the Na+, K+-ATPase alpha3 isoform disrupts Na+ interaction at the third Na+ site.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Mechanism of Rescue of NaInternational journal of molecular sciences · 2026Article
- On the mechanism of hypomagnesemia with treatment-resistant seizures caused by variants of the Na+,K+-ATPase α1 subunit (ATP1A1).The Journal of general physiology · 2026Article
- Non-hyperbolic enzyme kinetics: the case of P-type ATPases.Biophysical reviews · 2025Review
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- A Na pump with reduced stoichiometry is up-regulated by brine shrimp in extreme salinities.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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- The role ofFrontiers in cellular neuroscience · 2023Review
- Temperature instability of a mutation at a multidomain junction in Na,K-ATPase isoform ATP1A3 (p.Arg756His) produces a fever-induced neurological syndrome.The Journal of biological chemistry · 2023Article
- Structure and function of HNature communications · 2022Article
- Disease mutations of human α3 NaPNAS nexus · 2022Article
- The NaThe Journal of biological chemistry · 2022Article
- Article
- Diseases caused by mutations in the NaAmerican journal of physiology. Cell physiology · 2021Review
- Alternating Hemiplegia of Childhood: Understanding the Genotype-Phenotype Relationship of ATP1A3 Variations.The application of clinical genetics · 2020Review
- Factors in the disease severity of ATP1A3 mutations: Impairment, misfolding, and allele competition.Neurobiology of disease · 2019Article
- Genotype-structure-phenotype relationships diverge in paralogsNeurology. Genetics · 2019Review
- Distinct pH dependencies of NaThe Journal of biological chemistry · 2018Article
- Glutamate Water Gates in the Ion Binding Pocket of NaScientific reports · 2017Article
- Article
- Importance of a Potential Protein Kinase A Phosphorylation Site of Na+,K+-ATPase and Its Interaction Network for Na+ Binding.The Journal of biological chemistry · 2016Article
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5 authors.
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Abstract
Rapid-onset dystonia parkinsonism (RDP), a rare neurological disorder, is caused by mutation of the neuron-specific alpha3-isoform of Na(+), K(+)-ATPase. Here, we present the functional consequences of RDP mutation D923N. Relative to the wild type, the mutant exhibits a remarkable approximately 200-fold reduction of Na(+) affinity for activation of phosphorylation from ATP, reflecting a defective interaction of the E(1) form with intracellular Na(+). This is the largest effect on Na(+) affinity reported so far for any Na(+), K(+)-ATPase mutant. D923N also affects the interaction with extracellular Na(+) normally driving the E(1)P to E(2)P conformational transition backward. However, no impairment of K(+) binding was observed for D923N, leading to the conclusion that Asp(923) is specifically associated with the third Na(+) site that is selective toward Na(+). The crystal structure of the Na(+), K(+)-ATPase in E(2) form shows that Asp(923) is located in the cytoplasmic half of transmembrane helix M8 inside a putative transport channel, which is lined by residues from the transmembrane helices M5, M7, M8, and M10 and capped by the C terminus, recently found involved in recognition of the third Na(+) ion. Structural modeling of the E(1) form of Na(+), K(+)-ATPase based on the Ca(2+)-ATPase crystal structure is consistent with the hypothesis that Asp(923) contributes to a site binding the third Na(+) ion. These results in conjunction with our previous findings with other RDP mutants suggest that a selective defect in the handling of Na(+) may be a general feature of the RDP disorder.
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