A role for His155 in binding of human prion peptide144-167 to immobilised prion protein

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 compri...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-10, Vol.362 (3), p.695-699
Main Authors: Hesp, J Richard, Raven, Neil D H, Sutton, J Mark
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Circular Dichroism
Diethyl Pyrocarbonate - chemistry
Dose-Response Relationship, Drug
Histidine - chemistry
Humans
Hydrogen-Ion Concentration
Prions - chemistry
Protein Binding
Protein Conformation
Protein Folding
Protein Structure, Secondary
Recombinant Proteins - chemistry
Surface Plasmon Resonance
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Summary: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 alpha helix 1-beta 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).
ISSN:0006-291X
DOI:10.1016/j.bbrc.2007.08.050