A thermodynamic approach to the conformational preferences of the 180-195 segment derived from the human prion protein alpha2-helix.
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.
Ronga
Luisa
L
Dipartimento delle Scienze Biologiche and C.I.R.Pe.B., Università Federico II di Napoli, Naples, Italy.
Palladino
Pasquale
P
Ragone
Raffaele
R
Benedetti
Ettore
E
Rossi
Filomena
F
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
D010446:Peptide Fragments; D011328:Prions