NR AOHZ
AU Wong,B.S.; Li,R.; Sassoon,J.; Kang,S.C.; Liu,T.; Pan,T.; Greenspan,N.S.; Wisniewski,T.; Brown,D.R.; Sy,M.S.
TI Mapping the antigenicity of copper-treated cellular prion protein with the scrapie isoform
QU Cellular and Molecular Life Science 2003 Jun; 60(6): 1224-34
PT journal article
AB When recombinant and cellular prion protein (PrPc) binds copper, it acquires properties resembling the scrapie isoform (PrPsc), namely protease resistance, detergent insolubility and increased beta sheet content. However, whether the conformations of PrPc induced by copper and PrPsc are similar has not been studied in great detail. Here, we use a panel of seven monoclonal antibodies to decipher the epitopes on full-length mouse PrPc that are affected by exogenous copper, and to compare the antigenicity of the copper-treated full-length PrPc with the full-length PrPsc present in scrapie-infected mouse brains. In the presence of copper, we found that epitopes along residues 115-130 and 153-165 become more accessible on PrPc. These regions correspond to the two beta sheet strands in recombinant PrP and they were proposed to be important for prion conversion. However, when we compared the antibody-binding patterns between full-length PrPc with full-length PrPsc and between copper-treated full-length PrPc with full-length PrPsc, antibody binding to residues 143-155 and 175-185 was consistently increased on PrPsc. Collectively, our results suggest that copper-treated full-length PrPc does not resemble full-length PrPsc, despite acquiring PrPsc-like properties. In addition, since each full-length protein reacts distinctively to some of the antibodies, this binding pattern could discriminate between PrPc and PrPsc.
MH Animal; Antibodies, Monoclonal; Binding Sites; Brain Chemistry; Comparative Study; Copper/*pharmacology; Epitope Mapping; In Vitro; Mice; Mice, Knockout; PrPc Proteins/chemistry/*drug effects/*immunology; PrPsc Proteins/chemistry/*immunology; Protein Conformation/drug effects; Recombinant Proteins/chemistry/drug effects/immunology; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.
AD Institute of Pathology (BRB 933), Case Western Reserve University, School of Medicine, 10900 Euclid Ave., Cleveland, Ohio 44106, USA
SP englisch
PO Schweiz