Effect of salts on the structural behavior of hPrP α2‐helix‐derived analogues: the counterion perspective

Abstract

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.

Kosmotropic Anions Promote Conversion of Recombinant Prion Protein into a PrPSc-Like Misfolded Form

“…Protein-stabilizing salts have been classically shown to affect fibril formation in many amyloid systems [27], [29], [41]–[45]. In most cases, the lag phase of the process is accelerated at high concentrations of anions in an ion-specific manner that follows the Hofmeister series [26], [27], [29], [42]–[44], indicating a predominance of protein-water-ion interactions [43].…”

MACI - a new era?

“…Basad et al [69], Kon et al[70], and Visna et al[71] compared various types of MACI to marrow stimulation techniques. Basad et al and Visna et al found the MACI procedure to be superior to marrow stimulation techniques at short-term follow-up (1 to 2 years)[70,71].…”

“…Basad et al [69], Kon et al[70], and Visna et al[71] compared various types of MACI to marrow stimulation techniques. Basad et al and Visna et al found the MACI procedure to be superior to marrow stimulation techniques at short-term follow-up (1 to 2 years)[70,71]. Kon et al noted some deterioration of microfracture results between 2 and 5 years post-operative, while MACI results were unchanged[69], Bartlett et al compared MACI with traditional ACI and noted no significant differences between the two groups[45].…”

Conformational Diseases and Structure-Toxicity Relationships: Lessons from Prion-Derived Peptides

“…This may occur because ions are generally manipulated through the use of salts, and experiments have not always been designed so that it can be unequivocally perceived which species causes which modification [52]. In conclusion, most data suggest that copper ions may play a role in toxicity of amyloidogenic and/or fibrillogenic proteins, also indicating that a region of PrP C other than PrP[106-126] may be involved in neurotoxicity.…”

“…Most recently, we have shown that the conformational properties of two 2-helix-derived analogues can be even affected by anion identity. Large differences in CD spectra of both peptides were rationalized via the ion charge density dependence typical of Hofmeister effects [52]. Fig.…”