ArticleThe Journal of biological chemistry2011
Difference in stability of the N-domain underlies distinct intracellular properties of the E1064A and H1069Q mutants of copper-transporting ATPase ATP7B.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Wilson disease-causing mutations in the carboxyl terminus of ATP7B regulates its localization and Golgi exit selectively in the unpolarized cells.Metallomics : integrated biometal science · 2023Pooled it
- Evaluation of the Relationship Between Neurologic Manifestations and Genetic Mutations in Wilson's Disease with Next-Generation Sequencing.Diagnostics (Basel, Switzerland) · 2025Article
- Functional Screen of Wilson Disease ATP7B Variants Reveals Residual Transport Activities.Human mutation · 2025Article
- Aberrant copper metabolism and hepatic inflammation cause neurological manifestations in a mouse model of Wilson's disease.Journal of neuroinflammation · 2024Article
- Epidemiology of Wilson's Disease and Pathogenic Variants of theInternational journal of molecular sciences · 2024Review
- Response of Fibroblasts from Menkes' and Wilson's Copper Metabolism-Related Disorders to Ionizing Radiation: Influence of the Nucleo-Shuttling of the ATM Protein Kinase.Biomolecules · 2023Article
- Management Perspective of Wilson's Disease: Early Diagnosis and Individualized Therapy.Current neuropharmacology · 2021Article
- A case of Wilson disease with the ATP7B mutation presenting movement disorders.Surgical neurology international · 2021Article
- Analysis of Wilson disease mutations revealed that interactions between different ATP7B mutants modify their properties.Scientific reports · 2020Article
- Factors in the disease severity of ATP1A3 mutations: Impairment, misfolding, and allele competition.Neurobiology of disease · 2019Article
- Genetics and epigenetic factors of Wilson disease.Annals of translational medicine · 2019Review
- Characterization of the most frequent ATP7B mutation causing Wilson disease in hepatocytes from patient induced pluripotent stem cells.Scientific reports · 2018Article
- The genetics of Wilson disease.Handbook of clinical neurology · 2017Review
- Differential phosphorylation-based regulation of αB-crystallin chaperone activity for multipass transmembrane proteins.Biochemical and biophysical research communications · 2016Article
- Currently Clinical Views on Genetics of Wilson's Disease.Chinese medical journal · 2015Review
- Mapping the ATP binding site in the plasma membrane H(+)-ATPase from Kluyveromyces lactis.Journal of fluorescence · 2014Article
- Modifying factors and phenotypic diversity in Wilson's disease.Annals of the New York Academy of Sciences · 2014Review
- Distinct phenotype of a Wilson disease mutation reveals a novel trafficking determinant in the copper transporter ATP7B.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Intestinal expression of metal transporters in Wilson's disease.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2013Article
- Golgi in copper homeostasis: a view from the membrane trafficking field.Histochemistry and cell biology · 2013Review
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Authors and funding
5 authors at 2 institutions in 2 countries.
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Abstract
Wilson disease (WD) is a disorder of copper metabolism caused by mutations in the Cu-transporting ATPase ATP7B. WD is characterized by significant phenotypic variability, the molecular basis of which is poorly understood. The E1064A mutation in the N-domain of ATP7B was previously shown to disrupt ATP binding. We have now determined, by NMR, the structure of the N-domain containing this mutation and compared properties of E1064A and H1069Q, another mutant with impaired ATP binding. The E1064A mutation does not change the overall fold of the N-domain. However, the position of the α1,α2-helical hairpin (α-HH) that houses Glu(1064) and His(1069) is altered. The α-HH movement produces a more open structure compared with the wild-type ATP-bound form and misaligns ATP coordinating residues, thus explaining complete loss of ATP binding. In the cell, neither the stability nor targeting of ATP7B-E1064A to the trans-Golgi network differs significantly from the wild type. This is in a contrast to the H1069Q mutation within the same α-HH, which greatly destabilizes protein both in vitro and in cells. The difference between two mutants can be linked to a lower stability of the α-HH in the H1069Q variant at the physiological temperature. We conclude that the structural stability of the N-domain rather than the loss of ATP binding plays a defining role in the ability of ATP7B to reach the trans-Golgi network, thus contributing to phenotypic variability in WD.
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