Avtor/Urednik		Kovač, Valerija; Hafner Bratkovič, Iva; Čurin-Šerbec, Vladka
Naslov		Anchorless forms of prion protein - Impact of truncation on structure destabilization and prion protein conversion
Tip		članek
Vol. in št.		Letnik 481, št. 1/2
Leto izdaje		2016
Obseg		str. 1-6
ISSN		0006-291X - Biochemical and biophysical research communications
Jezik		eng
Abstrakt		Prion diseases are a group of fatal neurodegenerative diseases caused by scrapie form of prion protein, PrPSc. Prion protein (PrP) is bound to the cell via glycophosphatidylinositol (GPI) anchor. The role of GPI anchor in PrPSc 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.
Proste vsebinske oznake		prionski protein nevrodegenerativne bolezni oblike prion protein neurodegenerative diseases forms