ArticleStructure (London, England : 1993)2016
Interaction between Prion Protein's Copper-Bound Octarepeat Domain and a Charged C-Terminal Pocket Suggests a Mechanism for N-Terminal Regulation.
Article in Structure (London, England : 1993), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 84 citations in OpenAlex.
- Large-scale protein conformational transitions revealed by weighted ensemble simulations and EPR.Chemical science · 2026Article
- The structure of complexes between zinc(ii) cations and histidine-rich repeats from the unstructured N-terminal domain of human prion protein.RSC advances · 2025Review
- Segmental Isotope Labeling of the Prion Protein: Identification of a Key Residue for Copper-Mediated Interdomain Structure.ACS chemical biology · 2025Article
- Soluble N-terminal region of prion protein causes rapid neurodegeneration in prion disease.Science advances · 2025Article
- Mutant prion protein enhances NMDA receptor activity, activates PKC, and triggers rapid excitotoxicity in mice.The Journal of clinical investigation · 2025Article
- A Copper-Binding Peptide with Therapeutic Potential against Alzheimer's Disease: From the Blood-Brain Barrier to Metal Competition.ACS chemical neuroscience · 2025Article
- Review
- Direct observation of negative cooperativity in a detoxification enzyme at the atomic level by Electron Paramagnetic Resonance spectroscopy and simulation.Protein science : a publication of the Protein Society · 2023Article
- Prion propagation and cellular dysfunction in prion disease: Disconnecting the dots.PLoS pathogens · 2023Article
- Ultrafast Bioorthogonal Spin-Labeling and Distance Measurements in Mammalian Cells Using Small, Genetically Encoded Tetrazine Amino Acids.Journal of the American Chemical Society · 2023Article
- Prion Protein Octarepeat Domain Forms Transient β-Sheet Structures upon Residue-Specific Binding to Cu(II) and Zn(II) Ions.Biochemistry · 2023Article
- Rapid ex vivo reverse genetics identifies the essential determinants of prion protein toxicity.Brain pathology (Zurich, Switzerland) · 2023Article
- Ultra-Fast Bioorthogonal Spin-Labeling and Distance Measurements in Mammalian Cells Using Small, Genetically Encoded Tetrazine Amino Acids.bioRxiv : the preprint server for biology · 2023Article
- Structural and dynamical determinants of a β-sheet-enriched intermediate involved in amyloid fibrillar assembly of human prion protein.Chemical science · 2022Article
- Cu(Proline)Molecules (Basel, Switzerland) · 2022Article
- Prion protein with a mutant N-terminal octarepeat region undergoes cobalamin-dependent assembly into high-molecular weight complexes.The Journal of biological chemistry · 2022Article
- Melatonin: Regulation of Prion Protein Phase Separation in Cancer Multidrug Resistance.Molecules (Basel, Switzerland) · 2022Review
- EPR of copper centers in the prion protein.Methods in enzymology · 2022Article
- Membrane Domain Localization and Interaction of the Prion-Family Proteins, Prion and Shadoo with Calnexin.Membranes · 2021Article
- Zn(II) binding causes interdomain changes in the structure and flexibility of the human prion protein.Scientific reports · 2021Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Copper plays a critical role in prion protein (PrP) physiology. Cu(2+) binds with high affinity to the PrP N-terminal octarepeat (OR) domain, and intracellular copper promotes PrP expression. The molecular details of copper coordination within the OR are now well characterized. Here we examine how Cu(2+) influences the interaction between the PrP N-terminal domain and the C-terminal globular domain. Using nuclear magnetic resonance and copper-nitroxide pulsed double electron-electron resonance, with molecular dynamics refinement, we localize the position of Cu(2+) in its high-affinity OR-bound state. Our results reveal an interdomain cis interaction that is stabilized by a conserved, negatively charged pocket of the globular domain. Interestingly, this interaction surface overlaps an epitope recognized by the POM1 antibody, the binding of which drives rapid cerebellar degeneration mediated by the PrP N terminus. The resulting structure suggests that the globular domain regulates the N-terminal domain by binding the Cu(2+)-occupied OR within a complementary pocket.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.