Conformational properties of peptide fragments homologous to the 106-114 and 106-126 residues of the human prion protein: a CD and NMR spectroscopic study.
Two peptide fragments, corresponding to the amino acid residues 106-126 (PrP[Ac-106-126-NH(2)]) and 106-114 (PrP[Ac-106-114-NH(2)]) of the human prion protein have been synthesised in the acetylated and amide form at their N- and C-termini, respectively. The conformational preferences of PrP[Ac-106-126-NH(2)] and PrP[Ac-106-114-NH(2)] were investigated using CD and NMR spectroscopy. CD results showed that PrP[Ac-106-126-NH(2)] mainly adopts an alpha-helical conformation in TFE-water mixture and in SDS micelles, while a predominantly random structure is observed in aqueous solution. The shorter PrP[Ac-106-114-NH(2)] fragment showed similar propensities when investigated under the same experimental conditions as those employed for PrP[Ac-106-126-NH(2)]. From CD experiments at different SDS concentrations, an alpha-helix/beta-sheet conformational transition was only observed in the blocked PrP[Ac-106-126-NH(2)] sequence. The NMR analysis confirmed the helical nature of PrP[Ac-106-126-NH(2)] in the presence of SDS micelles. The shorter PrP[Ac-106-114-NH(2)] manifested a similar behaviour. The results as a whole suggest that both hydrophobic effects and electrostatic interactions play a significant role in the formation and stabilisation of ordered secondary structures in PrP[Ac-106-126-NH(2)].
Di Natale
Giuseppe
G
Dipartmento di Scienze Chimiche, Università di Catania, 95125 Catania.
Impellizzeri
Giuseppe
G
Pappalardo
Giuseppe
G
D002942:Circular Dichroism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D010446:Peptide Fragments / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012680:Sensitivity and Specificity
D010446:Peptide Fragments; D011328:Prions