NR AJER
AU Parchi,P.; Zou,W.Q.; Wang,W.; Brown,P.; Capellari,S.; Ghetti,B.; Kopp,N.; Schulz-Schaeffer,W.J.; Kretzschmar,H.A.; Head,M.W.; Ironside,J.W.; Gambetti,P.; Chen,S.G.
TI Genetic influence on the structural variations of the abnormal prion protein
QU Proceedings of the National Academy of Sciences of the United States of America 2000 Aug 29; 97(18): 10168-72
IA http://www.pnas.org/cgi/reprint/97/18/10168.pdf
PT journal article
AB Prion diseases are characterized by the presence of the abnormal prion protein PrPsc, which is believed to be generated by the conversion of the alpha-helical structure that predominates in the normal PrP isoform into a beta-sheet structure resistant to proteinase K (PK). In human prion diseases, two major types of PrPsc, type 1 and 2, can be distinguished based on the difference in electrophoretic migration of the PK-resistant core fragment. In this study, protein sequencing was used to identify the PK cleavage sites of PrPsc in 36 cases of prion diseases. We demonstrated two primary cleavage sites at residue 82 and residue 97 for type 1 and type 2 PrPsc, respectively, and numerous secondary cleavages distributed along the region spanning residues 74-102. Accordingly, we identify three regions in PrPsc: one N-terminal (residues 23-73) that is invariably PK-sensitive, one C-terminal (residues 103-231) that is invariably PK-resistant, and a third variable region (residues 74-102) where the site of the PK cleavage, likely reflecting the extent of the beta-sheet structure, varies mostly as a function of the PrP genotype at codon 129.
MH *Brain Chemistry; Codon; Creutzfeldt-Jakob Syndrome/*genetics; Endopeptidase K; Human; Kuru/*genetics; Peptide Fragments/chemistry; PrPsc Proteins/chemistry/*genetics; Protein Conformation; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; *Variation (Genetics)
AD Piero Parchi, Wenquan Zou, Wen Wang, Sabina Capellari, Pierluigi Gambetti (pxg13@po.cwru.edu), Shu G. Chen (sxc59@po.cwru.edu), Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA; Paul Brown, Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892, USA; Bernardino Ghetti, Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202, USA; Nicolas Kopp, Hopital Neurologique Pierre Wertheimer, Lyon 69003, France; Walter J. Schulz-Schaeffer, Hans A. Kretzschmar, Institut für Neuropathologie, Georg-August-Universitat Göttingen, 37075 Göttingen, Germany; Mark W. Head, James W. Ironside, Creutzfeldt-Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, England; Piero Parchi, Sabina Capellari, Present address: Department of Neurological Sciences, University of Bologna, Via Foscolo 7, 40123 Bologna, Italy
SP englisch
PO USA
EA pdf-Datei und HTML-Version