ArticleScientific reports2015
The non-octarepeat copper binding site of the prion protein is a key regulator of prion conversion.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Prion propagation is controlled by discrete structural regions of PrP rather than overall stability.The Journal of biological chemistry · 2026Article
- Copper Coordination to the Prion Fragment (95-126): Implications for Neurodegenerative Diseases.International journal of molecular sciences · 2026Article
- Substitution of histidine 95 by tyrosine in the prion protein causes spontaneous neurodegeneration in transgenic mice.PLoS pathogens · 2025Article
- Comparing Prion Proteins Across Species: Is Zebrafish a Useful Model?Molecular neurobiology · 2025Review
- Copper coordination modulates prion conversion and infectivity in mammalian prion proteins.Prion · 2023Review
- Therapeutic strategies for identifying small molecules against prion diseases.Cell and tissue research · 2023Review
- Prion therapeutics: Lessons from the past.Prion · 2022Review
- The E3 Ubiquitin Ligase TRAF6 Interacts with the Cellular Prion Protein and Modulates Its Solubility and Recruitment to Cytoplasmic p62/SQSTM1-Positive Aggresome-Like Structures.Molecular neurobiology · 2022Article
- EPR of copper centers in the prion protein.Methods in enzymology · 2022Article
- Neurometals in the Pathogenesis of Prion Diseases.International journal of molecular sciences · 2021Review
- PrPFrontiers in molecular neuroscience · 2021Review
- Using NMR spectroscopy to investigate the role played by copper in prion diseases.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Review
- N-Terminal Regions of Prion Protein: Functions and Roles in Prion Diseases.International journal of molecular sciences · 2020Review
- Deciphering Copper Coordination in the Mammalian Prion Protein Amyloidogenic Domain.Biophysical journal · 2020Article
- Copper Binding Regulates Cellular Prion Protein Function.Molecular neurobiology · 2019Article
- Review
- Structural Determinants of the Prion Protein N-Terminus and Its Adducts with Copper Ions.International journal of molecular sciences · 2018Review
- Copper signalling: causes and consequences.Cell communication and signaling : CCS · 2018Review
- Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.PloS one · 2017Article
- Metal Dyshomeostasis and Their Pathological Role in Prion and Prion-Like Diseases: The Basis for a Nutritional Approach.Frontiers in neuroscience · 2017Review
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The conversion of the prion protein (PrP(C)) into prions plays a key role in transmissible spongiform encephalopathies. Despite the importance for pathogenesis, the mechanism of prion formation has escaped detailed characterization due to the insoluble nature of prions. PrP(C) interacts with copper through octarepeat and non-octarepeat binding sites. Copper coordination to the non-octarepeat region has garnered interest due to the possibility that this interaction may impact prion conversion. We used X-ray absorption spectroscopy to study copper coordination at pH 5.5 and 7.0 in human PrP(C) constructs, either wild-type (WT) or carrying pathological mutations. We show that mutations and pH cause modifications of copper coordination in the non-octarepeat region. In the WT at pH 5.5, copper is anchored to His96 and His111, while at pH 7 it is coordinated by His111. Pathological point mutations alter the copper coordination at acidic conditions where the metal is anchored to His111. By using in vitro approaches, cell-based and computational techniques, we propose a model whereby PrP(C) coordinating copper with one His in the non-octarepeat region converts to prions at acidic condition. Thus, the non-octarepeat region may act as the long-sought-after prion switch, critical for disease onset and propagation.
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