nad a22 4500 555301990 20190206082644.0 cr unu---uuuuu 190206e19971106xx s 000 0 eng 10.5167/uzh-167140 doi 10.1038/36337 doi (ZORA)oai:www.zora.uzh.ch:167140 570 ddc 630 ddc 9363892 pmid Prion (PrPSc)-specific epitope defined by a monoclonal antibody [Elektronische Daten] [C Korth, B Stierli, P Streit, M Moser, O Schaller, R Fischer, W Schulz-Schaeffer, H Kretzschmar, A Raeber, Ueli Braun, F Ehrensperger, S Hornemann, R Glockshuber, R Riek, M Billeter, K Wüthrich, B Oesch] restrictedAccess eu-repo Prions are infectious particles causing transmissible spongiform encephalopathies (TSEs). They consist, at least in part, of an isoform (PrPSc) of the ubiquitous cellular prion protein (PrPC). Conformational differences between PrPC and PrPSc are evident from increased beta-sheet content and protease resistance in PrPSc. Here we describe a monoclonal antibody, 15B3, that can discriminate between the normal and disease-specific forms of PrP. Such an antibody has been long sought as it should be invaluable for characterizing the infectious particle as well as for diagnosis of TSEs such as bovine spongiform encephalopathy (BSE) or Creutzfeldt-Jakob disease (CJD) in humans. 15B3 specifically precipitates bovine, murine or human PrPSc, but not PrPC, suggesting that it recognizes an epitope common to prions from different species. Using immobilized synthetic peptides, we mapped three polypeptide segments in PrP as the 15B3 epitope. In the NMR structure of recombinant mouse PrP, segments 2 and 3 of the 15B3 epitope are near neighbours in space, and segment 1 is located in a different part of the molecule. We discuss models for the PrPSc-specific epitope that ensure close spatial proximity of all three 15B3 segments, either by intermolecular contacts in oligomeric forms of the prion protein or by intramolecular rearrangement. Department of Farm Animals zora Korth C. joint author Stierli B. joint author Streit P. joint author Moser M. joint author Schaller O. joint author Fischer R. joint author Schulz-Schaeffer W. joint author Kretzschmar H. joint author Raeber A. joint author Braun Ueli joint author Ehrensperger F. joint author Hornemann S. joint author Glockshuber R. joint author Riek R. joint author Billeter M. joint author Wüthrich K. joint author Oesch B. joint author Nature 390(6655):74-77 https://www.zora.uzh.ch/id/eprint/167140/1/36337.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/167140/1/36337.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Korth C. joint author ZORA 700 1- Stierli B. joint author ZORA 700 1- Streit P. joint author ZORA 700 1- Moser M. joint author ZORA 700 1- Schaller O. joint author ZORA 700 1- Fischer R. joint author ZORA 700 1- Schulz-Schaeffer W. joint author ZORA 700 1- Kretzschmar H. joint author ZORA 700 1- Raeber A. joint author ZORA 700 1- Braun Ueli joint author ZORA 700 1- Ehrensperger F. joint author ZORA 700 1- Hornemann S. joint author ZORA 700 1- Glockshuber R. joint author ZORA 700 1- Riek R. joint author ZORA 700 1- Billeter M. joint author ZORA 700 1- Wüthrich K. joint author ZORA 700 1- Oesch B. joint author ZORA 773 0- Nature 390(6655):74-77 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article restrictedAccess