title: Distinct morphological and electrophysiological properties of an elk prion peptide.
abstract: A key event in prion diseases is the conversion of the prion protein (PrP) from its native α-helical conformation to a misfolded, β-sheet rich conformation. Thus, preventing or reversing PrP misfolding could provide a means to disrupt prion disease progression and transmission. However, determining the structure of misfolded PrP has been notoriously difficult due to its inherent heterogeneity and aggregation behavior. For these reasons, simplified peptide fragments have been used as models that recapitulate characteristics of full-length PrP, such as amyloid-like aggregation and fibril formation, and in vitro toxicity. We provide a biochemical and structural comparison of PrP(127-147) peptides from elk, bovine and hamster using electrophysiology, electron microscopy and fluorescence. Our results demonstrate that the PrP(127-147) peptides adopt distinct populations of fibril structures. In addition, the elk PrP(127-147) peptide is unique in its ability to enhance Thioflavin T fluorescence and its ability to modulate neuronal ion channel conductances.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2H7.
authors.forename: John Paul
authors.initials: JP
authors.lastname: Glaves
authors.forename: Przemek A
authors.initials: PA
authors.lastname: Gorski
authors.forename: Kwai
authors.initials: K
authors.lastname: Alier
authors.forename: Li
authors.initials: L
authors.lastname: Ma
authors.forename: Ludovic
authors.initials: L
authors.lastname: Renault
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Primeau
authors.forename: Jack H
authors.initials: JH
authors.lastname: Jhamandas
authors.forename: Howard S
authors.initials: HS
authors.lastname: Young
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D006224:Cricetinae; D003670:Deer; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D017096:Prion Diseases; D011328:Prions / Q000737:chemistry*; D017510:Protein Folding; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D010446:Peptide Fragments; D010455:Peptides; D011328:Prions