title: Conformational properties of the prion octa-repeat and hydrophobic sequences.
abstract: We have used circular dichroism to study synthetic peptides from two important regions of the prion protein: the N-terminal octa-repeat domain and a highly conserved hydrophobic section. Our results show that the octa-repeat sequence in free solution can adopt a non-random, extended conformation with properties similar to the poly-L-proline type II left-handed helix. We also show that the conformation can be changed by temperature, organic solvents (e.g. acetonitrile) and on binding to phospholipid vesicles. We compared CD data from two peptides corresponding to the hydrophobic region between residues 106 and 136 which contained either methionine or valine at position 129. This variation represents a common polymorphism in humans which has been shown to influence predisposition towards iatrogenic and sporadic CJD. There was no detectable difference between the CD spectra of these peptides irrespective of the solvent conditions we used.
authors.affiliation: Department of Biochemistry, School of Medical Sciences, University of Bristol, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Smith
authors.forename: A F
authors.initials: AF
authors.lastname: Drake
authors.forename: B A
authors.initials: BA
authors.lastname: Banfield
authors.forename: G B
authors.initials: GB
authors.lastname: Bloomberg
authors.forename: M S
authors.initials: MS
authors.lastname: Palmer
authors.forename: A R
authors.initials: AR
authors.lastname: Clarke
authors.forename: J
authors.initials: J
authors.lastname: Collinge
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D002942:Circular Dichroism; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017354:Point Mutation; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D012091:Repetitive Sequences, Nucleic Acid; D012995:Solubility; D012997:Solvents
chemical_list: D010455:Peptides; D011328:Prions; D012997:Solvents