title: A thermodynamic approach to the conformational preferences of the 180-195 segment derived from the human prion protein alpha2-helix.
abstract: On consideration that intrinsic structural weakness could affect the segment spanning the alpha2-helical residues 173-195 of the PrP, we have investigated the conformational stabilities of some synthetic Ala-scanned analogs of the peptide derived from the 180-195 C-terminal sequence, using a novel approach whose theoretical basis originates from protein thermodynamics. Even though a quantitative comparison among peptides could not be assessed to rank them according to the effect caused by single amino acid substitution, as a general trend, all peptides invariably showed an appreciable preference for an alpha-type organization, consistently with the fact that the wild-type sequence is organized as an alpha-helix in the native protein. Moreover, the substitution of whatever single amino acid in the wild-type sequence reduced the gap between the alpha- and the beta-propensity, invariably enhancing the latter, but in any case this gap was larger than that evaluated for the full-length alpha2-helix-derived peptide. It appears that the low beta-conformation propensity of the 180-195 region depends on the simultaneous presence of all of the Ala-scanned residues, indirectly confirming that the N-terminal 173-179 segment could play a major role in determining the chameleon conformational behavior of the entire 173-195 region in the PrP.
authors.affiliation: Dipartimento delle Scienze Biologiche and C.I.R.Pe.B., Università Federico II di Napoli, Naples, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ronga
authors.forename: Pasquale
authors.initials: P
authors.lastname: Palladino
authors.forename: Raffaele
authors.initials: R
authors.lastname: Ragone
authors.forename: Ettore
authors.initials: E
authors.lastname: Benedetti
authors.forename: Filomena
authors.initials: F
authors.lastname: Rossi
mesh_terms: D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry*; D011328:Prions / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D010446:Peptide Fragments; D011328:Prions