ArticleThe Journal of biological chemistry2011
The lumenal loop Met672-Pro707 of copper-transporting ATPase ATP7A binds metals and facilitates copper release from the intramembrane sites.
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.
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Who cites it
23 citing papers in PubMed.
- Copper homeostasis and cuproptosis in central nervous system diseases.Cell death & disease · 2024Review
- The mitochondrial CuFrontiers in molecular biosciences · 2022Article
- Review
- Retromer retrieves the Wilson disease protein ATP7B from endolysosomes in a copper-dependent manner.Journal of cell science · 2020Article
- Single nucleotide polymorphisms in the human ATP7B gene modify the properties of the ATP7B protein.Metallomics : integrated biometal science · 2019Article
- Review
- Exploiting the vulnerable active site of a copper-only superoxide dismutase to disrupt fungal pathogenesis.The Journal of biological chemistry · 2019Article
- A Luminal Loop of Wilson Disease Protein Binds Copper and Is Required for Protein Activity.Biophysical journal · 2018Article
- Identification of Two Conserved Residues Involved in Copper Release from Chloroplast PIB-1-ATPases.The Journal of biological chemistry · 2016Article
- Bacterial Cu(+)-ATPases: models for molecular structure-function studies.Metallomics : integrated biometal science · 2016Review
- pH-regulated metal-ligand switching in the HM loop of ATP7A: a new paradigm for metal transfer chemistry.Metallomics : integrated biometal science · 2016Article
- Adaptor Protein-1 Complex Affects the Endocytic Trafficking and Function of Peptidylglycine α-Amidating Monooxygenase, a Luminal Cuproenzyme.The Journal of biological chemistry · 2015Article
- Counteract of bone marrow of blotchy mice against the increases of plasma copper levels induced by high-fat diets in LDLR-/- mice.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2015Article
- Copper-transporting P-type ATPases use a unique ion-release pathway.Nature structural & molecular biology · 2014Article
- An expanding range of functions for the copper chaperone/antioxidant protein Atox1.Antioxidants & redox signaling · 2013Review
- HHM motif at the CuH-site of peptidylglycine monooxygenase is a pH-dependent conformational switch.Biochemistry · 2013Article
- Biometals in rare neurodegenerative disorders of childhood.Frontiers in aging neuroscience · 2013Article
- Distinctive features of catalytic and transport mechanisms in mammalian sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) and Cu+ (ATP7A/B) ATPases.The Journal of biological chemistry · 2012Article
- A structural model of the copper ATPase ATP7B to facilitate analysis of Wilson disease-causing mutations and studies of the transport mechanism.Metallomics : integrated biometal science · 2012Article
- Lumenal loop M672-P707 of the Menkes protein (ATP7A) transfers copper to peptidylglycine monooxygenase.Journal of the American Chemical Society · 2012Article
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7 authors.
Funding
Abstract
The copper-transporting ATPase ATP7A has an essential role in human physiology. ATP7A transfers the copper cofactor to metalloenzymes within the secretory pathway; inactivation of ATP7A results in an untreatable neurodegenerative disorder, Menkes disease. Presently, the mechanism of ATP7A-mediated copper release into the secretory pathway is not understood. We demonstrate that the characteristic His/Met-rich segment Met(672)-Pro(707) (HM-loop) that connects the first two transmembrane segments of ATP7A is important for copper release. Mutations within this loop do not prevent the ability of ATP7A to form a phosphorylated intermediate during ATP hydrolysis but inhibit subsequent dephosphorylation, a step associated with copper release. The HM-loop inserted into a scaffold protein forms two structurally distinct binding sites and coordinates copper in a mixed His-Met environment with an ∼2:1 stoichiometry. Binding of either copper or silver, a Cu(I) analog, induces structural changes in the loop. Mutations of 4 Met residues to Ile or two His-His pairs to Ala-Gly decrease affinity for copper. Altogether, the data suggest a two-step process, where copper released from the transport sites binds to the first His(Met)(2) site, triggering a structural change and binding to a second 2-coordinate His-His or His-Met site. We also show that copper binding within the HM-loop stabilizes Cu(I) and protects it from oxidation, which may further aid the transfer of copper from ATP7A to acceptor proteins. The mechanism of copper entry into the secretory pathway is discussed.
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