Anchorless forms of prion protein – Impact of truncation on structure destabilization and prion protein conversion
- Department for the Production of Diagnostic Reagents and Research & R&D Service, Blood Transfusion Centre of Slovenia, Šlajmerjeva 6, SI-1000, Ljubljana (Slovenia)
- Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, SI-1000, Ljubljana (Slovenia)
Prion diseases are a group of fatal neurodegenerative diseases caused by scrapie form of prion protein, PrP{sup Sc}. Prion protein (PrP) is bound to the cell via glycophosphatidylinositol (GPI) anchor. The role of GPI anchor in PrP{sup Sc} replication and propagation remains unclear. It has been shown that anchorless and truncated PrP accelerate the formation and propagation of prions in vivo and further increases the risk for transmission of prion diseases among species. To explain the role of anchorless forms of PrP in the development of prion diseases, we have prepared five C-terminal PrP truncated variants, determined their thermodynamic properties and analyzed the kinetics of conversion into amyloid fibrils. According to our results thermodynamic and kinetic properties are affected both by pH and truncation. We have shown that the shortest variant was the most destabilized and converted faster than other variants in acidic pH. Other variants converted with longer lag time of fibrillization than WT despite comparable or even decreased stability in acidic pH. Our results indicate that even the change in length for 1 amino acid residue can have a profound effect on in vitro conversion. - Highlights: • Truncation effects prion protein stability and fibrillization properties. • Protein destabilization and fibrillization properties are affected by pH and truncation. • Important intramolecular interactions between loop β{sub 2}−α{sub 2} and C-terminus of helix α{sub 3}.
- OSTI ID:
- 22696719
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 481, Issue 1-2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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