A role for His 155 in binding of human prion peptide 144–167 to immobilised prion protein

Abstract

The interactions and conformational changes that lead to the conversion of the normal prion protein (PrP c) to its pathogenic form, PrP sc, are still being elucidated. Using Surface Plasma Resonance (SPR), we provide evidence that a synthetic peptide (PrP 144–167) corresponding to residues comprising the α helix 1–β strand 2 domain of PrP c is able to interact and bind to immobilised recombinant human PrP (rHuPrP) in a dose-dependent manner. The interaction is pH dependent with an increase in binding observed as the pH is lowered, particularly between pH 6.5 and pH 5.5 suggesting a specific role for His 155 in the interaction, confirmed by covalent modification of this residue in the peptide with diethylpyrocarbonate (DEPC). Circular dichroism analysis of PrP 144–167 revealed no secondary structure motifs across the pH range investigated. Possible pH related structural changes of immobilised rHuPrP are also discussed with regard to the increased affinity for PrP 144–167.