Exp Mol Med.  2013 Aug;45(8):e34.

Characterizing affinity epitopes between prion protein and beta-amyloid using an epitope mapping immunoassay

• Kang M
• Kim SY
• An SS
• Ju YR

Abstract

Cellular prion protein, a membrane protein, is expressed in all mammals. Prion protein is also found in human blood as an anchorless protein, and this protein form is one of the many potential sources of misfolded prion protein replication during transmission. Many studies have suggested that beta-amyloid1-42 oligomer causes neurotoxicity associated with Alzheimer's disease, which is mediated by the prion protein that acts as a receptor and regulates the hippocampal potentiation. The prevention of the binding of these proteins has been proposed as a possible preventative treatment for Alzheimer's disease; therefore, a greater understanding of the binding hot-spots between the two molecules is necessary. In this study, the epitope mapping immunoassay was employed to characterize binding epitopes within the prion protein and complementary epitopes in beta-amyloid. Residues 23-39 and 93-119 in the prion protein were involved in binding to beta-amyloid1-40 and 1-42, and monomers of this protein interacted with prion protein residues 93-113 and 123-166. Furthermore, beta-amyloid antibodies against the C-terminus detected bound beta-amyloid1-42 at residues 23-40, 104-122 and 159-175. beta-Amyloid epitopes necessary for the interaction with prion protein were not determined. In conclusion, charged clusters and hydrophobic regions of the prion protein were involved in binding to beta-amyloid1-40 and 1-42. The 3D structure appears to be necessary for beta-amyloid to interact with prion protein. In the future, these binding sites may be utilized for 3D structure modeling, as well as for the pharmaceutical intervention of Alzheimer's disease.

Keyword

Alzheimer's disease; amyloid-beta; epitope mapping; ligand; prion protein

MeSH Terms

Amyloid beta-Peptides/*metabolism
Electrophoresis
Enzyme-Linked Immunosorbent Assay
*Epitope Mapping
Epitopes/*metabolism
Humans
*Immunoassay
Prions/*metabolism
Protein Binding
Recombinant Proteins/metabolism
Amyloid beta-Peptides
Epitopes
Prions
Recombinant Proteins