NR AOVQ
AU Leclerc,E.; Ball,H.L.; Safar,J.G.; Serban,H.; Prusiner,S.B.; Burton,D.R.; Williamson,A.
TI Copper induces conformational changes in the N-terminal part of cell-surface PrPc
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-117
PT Konferenz-Poster
AB Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a group of fatal neurodegenerative conditions caused by misfolding of the cellular prion protein (PrPc). In vitro studies have shown that PrPc binds copper via a conserved octarepeat region lying within the unstructured N-terminal segment of the protein. The significance of copper binding in normal and abnormal PrP metabolism remains unclear. Here, specific antibodies recognizing different regions of PrP are used as probes to measure the effect of copper on the conformation of PrPc on the cell-surface. We find that antibody Fab fragments binding to linear epitopes located at the extreme N- or C-termini of PrPc (Fabs E123 and R1, recognizing residues 29-37 and 220-231, respectively), to the first a-helix of PrPc (Fab D18, recognizing residues 134-158), or to a linear epitope in the middle of the protein (Fab D13, recognizing residues 96-106) are relatively unaffected by the presence of copper. However, the binding of antibody Fab E149, recognizing a linear epitope (residues 72-86) within the octarepeat domain of PrP, is significantly reduced in the presence of copper, both in terms of its affinity and in the total number of available binding sites at the cell-surface. This observation provides evidence that copper can induce localized conformational change in cell-surface PrPc.
AD Estelle Leclerc, Dennis Burton, Anthony Williamson, The Scripps Research Institute, USA; Haydn Ball, Jiri Safar, Hana Serban, Stanley Prusiner, University of California San Francisco, USA
SP englisch
PO Deutschland