title: Copper induces conformational changes in the N-terminal part of cell-surface PrPC.
abstract: Prion diseases are caused by misfolding of the cellular prion protein, PrPC. In vitro studies have shown that PrP binds copper via the octarepeat region lying within the unstructured N-terminal segment of the protein, but the significance of copper in PrP metabolism remains unclear. Here, six specific antibodies recognizing different epitope regions of PrP were used to measure the effect of copper on the conformation of the molecule at the cell surface. Binding of an antibody, E149, to an epitope within the octarepeat domain of PrP is halved in the presence of copper, whereas binding of antibodies recognizing epitope motifs C-terminal to residue 90 of PrP remain relatively unaltered under equivalent conditions. These experiments strongly suggest that copper induces localized conformational change within the N-terminal portion of cell-surface PrPC.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: E
authors.initials: E
authors.lastname: Leclerc
authors.forename: H
authors.initials: H
authors.lastname: Serban
authors.forename: S B
authors.initials: SB
authors.lastname: Prusiner
authors.forename: D R
authors.initials: DR
authors.lastname: Burton
authors.forename: R A
authors.initials: RA
authors.lastname: Williamson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D003300:Copper / Q000494:pharmacology*; D006224:Cricetinae; D018604:Epitope Mapping; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D018621:PrPC Proteins / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D018621:PrPC Proteins; D003300:Copper