Prion Protein Aggregation Induced by Copper(II) and Heparan Sulfate. Pressure-dependent Switch of Reaction Pathways
| Autor: | Joan Torrent, Reinhard Lange, Driss El Moustaine |
|---|---|
| Přispěvatelé: | Mécanismes moléculaires dans les démences neurodégénératives (MMDN), Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL) |
| Rok vydání: | 2008 |
| Předmět: |
inorganic chemicals
0106 biological sciences Gene isoform PRP Scrapie SCRAPIE Fibril BINDING-SITES 01 natural sciences law.invention Glycosaminoglycan 03 medical and health sciences chemistry.chemical_compound AMYLOID FIBRILS RECOMBINANT law GLYCOSAMINOGLYCAN OCTAREPEAT DOMAIN Binding site 030304 developmental biology 0303 health sciences IN-VITRO General Chemistry Heparan sulfate In vitro [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biophysics high pressure CONVERSION chemistry Biochemistry prion protein copper PHYSICOCHEMICAL PROPERTIES Recombinant DNA Biophysics heparan sulfate 010606 plant biology & botany |
| Zdroj: | Zeitschrift fur Naturforschung B Zeitschrift fur Naturforschung B, Verlag der Zeitschrift Fuer Naturforschung, 2008, 63, pp.747-755. ⟨10.1515/znb-2008-0624⟩ |
| ISSN: | 1865-7117 0932-0776 |
| DOI: | 10.1515/znb-2008-0624 |
| Popis: | Copper ions (Cu2+) and heparan sulfate (HS) are suspected to act as regulatory agents in the conversion of cellular prion protein (PrPC) to its infectious isoform. However, the mechanism of this reaction is still largely unknown. Our previous report suggested multidimensional pathways for structural alterations of PrP, which may be modulated by high pressure (HP). Here we use HP to investigate the effects of Cu2+ and HS binding on PrP conformational changes and assembly. In the presence of Cu2+, amyloid fibrils are formed only under HP. In contrast, in the presence of HS, fibrils are formed at atmospheric pressure, but not under HP. Both compounds appear to compete for the same binding site, since HS-supported fibril formation is quenched by Cu2+. Inversely, Cu2+- mediated fibril formation under HP is inhibited by HS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|