ArticleProceedings of the National Academy of Sciences of the United States of America2006
Solution structure of the N-domain of Wilson disease protein: distinct nucleotide-binding environment and effects of disease mutations.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Clinical and Molecular Spectrum of Wilson Disease in the Arab World: A Systematic Review.Biochemical genetics · 2025Pooled it
- Functional Screen of Wilson Disease ATP7B Variants Reveals Residual Transport Activities.Human mutation · 2025Article
- Clinical and genetic characterization of patients with late onset Wilson's disease.NPJ genomic medicine · 2024Article
- Nano-Mediated Molecular Targeting in Diagnosis and Mitigation of Wilson Disease.Molecular neurobiology · 2024Review
- Article
- Copper binding leads to increased dynamics in the regulatory N-terminal domain of full-length human copper transporter ATP7B.PLoS computational biology · 2022Article
- At sixes and sevens: cryptic domain in the metal binding chain of the human copper transporter ATP7A.Biophysical journal · 2021Article
- Analysis of Wilson disease mutations revealed that interactions between different ATP7B mutants modify their properties.Scientific reports · 2020Article
- Review
- Case of Early-Onset Parkinson's Disease in a Heterozygous Mutation Carrier of theJournal of personalized medicine · 2019Article
- Copper regulates rest-activity cycles through the locus coeruleus-norepinephrine system.Nature chemical biology · 2018Article
- A glimpse into the regulation of the Wilson disease protein, ATP7B, sheds light on the complexity of mammalian apical trafficking pathways.Metallomics : integrated biometal science · 2018Review
- The Structure of Metal Binding Domain 1 of the Copper Transporter ATP7B Reveals Mechanism of a Singular Wilson Disease Mutation.Scientific reports · 2018Article
- The six metal binding domains in human copper transporter, ATP7B: molecular biophysics and disease-causing mutations.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2017Review
- The metal chaperone Atox1 regulates the activity of the human copper transporter ATP7B by modulating domain dynamics.The Journal of biological chemistry · 2017Article
- Structural Insights into the Nucleotide-Binding Domains of the P1B-type ATPases HMA6 and HMA8 from Arabidopsis thaliana.PloS one · 2016Article
- Wilson's disease: a comprehensive review of the molecular mechanisms.International journal of molecular sciences · 2015Review
- Interactions between metal-binding domains modulate intracellular targeting of Cu(I)-ATPase ATP7B, as revealed by nanobody binding.The Journal of biological chemistry · 2014Article
- Biochemical characterization of P-type copper ATPases.The Biochemical journal · 2014Review
- 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
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Wilson disease protein (ATP7B) is a copper-transporting P(1B)-type ATPase that regulates copper homeostasis and biosynthesis of copper-containing enzymes in human tissues. Inactivation of ATP7B or related ATP7A leads to severe neurodegenerative disorders, whereas their overexpression contributes to cancer cell resistance to chemotherapeutics. Copper-transporting ATPases differ from other P-type ATPases in their topology and the sequence of their nucleotide-binding domain (N-domain). To gain insight into the structural basis of ATP7B function, we have solved the structure of the ATP7B N-domain in the presence of ATP by using heteronuclear multidimensional NMR spectroscopy. The N-domain consists of a six-stranded beta-sheet with two adjacent alpha-helical hairpins and, unexpectedly, shows higher similarity to the bacterial K(+)-transporting ATPase KdpB than to the mammalian Ca(2+)-ATPase or Na(+),K(+)-ATPase. The common core structure of P-type ATPases is retained in the 3D fold of the N-domain; however, the nucleotide coordination environment of ATP7B within this fold is different. The residues H1069, G1099, G1101, I1102, G1149, and N1150 conserved in the P(1B)-ATPase subfamily contribute to ATP binding. Analysis of the frequent disease mutation H1069Q demonstrates that this mutation does not significantly affect the structure of the N-domain but prevents tight binding of ATP. The structure of the N-domain accounts for the disruptive effects of >30 known Wilson disease mutations. The unique features of the N-domain provide a structural basis for the development of specific inhibitors and regulators of ATP7B.
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