Effect of salts on the structural behavior of hPrP alpha2-helix-derived analogues: the counterion perspective.
Both theoretical studies and direct experimental evidence have emphasized the importance of electrostatic interactions in the general phenomenon of spontaneous amyloid fibril formation. A number of observations have recently spurred interest in the contribution of these interactions to the conformational behavior of the prion protein. In this paper, we show how salt addition and pH change can modify the conformation of two peptide analogues derived from the human prion protein helix 2 according to a Hofmeister-series-type dependence. Employment of various sodium salts allowed us to highlight the fact that chaotropic anions favor unstructured conformation, whereas kosmotropic anions promote the formation of compact structures like alpha-helix and beta-sheet, which may ultimately facilitate fibril formation. This finding should warn people engaged in ion-based research on prion and derived peptides about cation-bound effects, which have been almost exclusively investigated to date, being easily confounded with modifications that are actually caused by anion activity, thus leading researchers into misunderstand ion-specific effects. To avoid the common complication of ion confounding, it is highly desirable that experiments be designed so that the species causing the modification can be unequivocally perceived.
Ronga
Luisa
L
Dipartimento delle Scienze Biologiche, C.I.R.Pe.B, Università Federico II di Napoli and Istituto di Bioimmagini e Biostrutture, CNR, Via Mezzocannone 16, 80134 Napoli, Italy.
Palladino
Pasquale
P
Tizzano
Barbara
B
Marasco
Daniela
D
Benedetti
Ettore
E
Ragone
Raffaele
R
Rossi
Filomena
F
D000595:Amino Acid Sequence; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011328:Prions / Q000737:chemistry; D017433:Protein Structure, Secondary; D012492:Salts / Q000737:chemistry*; D055672:Static Electricity; D013431:Sulfates / Q000737:chemistry
D010455:Peptides; D011328:Prions; D012492:Salts; D013431:Sulfates; C012036:sodium sulfate