{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:07:42Z","timestamp":1791328062732,"version":"4.3.1"},"reference-count":29,"publisher":"National Academy of Sciences","issue":"18","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,8,29]]},"abstract":"<jats:p>\n                    Prion diseases are characterized by the presence of the abnormal prion protein PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    , which is believed to be generated by the conversion of the \u03b1-helical structure that predominates in the normal PrP isoform into a \u03b2-sheet structure resistant to proteinase K (PK). In human prion diseases, two major types of PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    , 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 PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    in 36 cases of prion diseases. We demonstrated two primary cleavage sites at residue 82 and residue 97 for type 1 and type 2 PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    , respectively, and numerous secondary cleavages distributed along the region spanning residues 74\u2013102. Accordingly, we identify three regions in PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    : one N-terminal (residues 23\u201373) that is invariably PK-sensitive, one C-terminal (residues 103\u2013231) that is invariably PK-resistant, and a third variable region (residues 74\u2013102) where the site of the PK cleavage, likely reflecting the extent of the \u03b2-sheet structure, varies mostly as a function of the PrP genotype at codon 129.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.18.10168","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:52Z","timestamp":1027680052000},"page":"10168-10172","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":264,"title":["Genetic influence on the structural variations of the abnormal prion protein"],"prefix":"10.1073","volume":"97","author":[{"given":"Piero","family":"Parchi","sequence":"first","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenquan","family":"Zou","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Brown","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Capellari","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardino","family":"Ghetti","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Kopp","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Schulz-Schaeffer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans A.","family":"Kretzschmar","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark W.","family":"Head","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James W.","family":"Ironside","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierluigi","family":"Gambetti","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu G.","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106; Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20892; Department of Pathology, Indiana University Medical Center, Indianapolis, IN 46202; H\u00f4pital Neurologique Pierre Wertheimer, Lyon 69003, France; Institut fur Neuropathologie, Georg-August-Universitat G\u00f6ttingen, 37075 G\u00f6ttingen, Germany; and Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,8,29]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-199508000-00007"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1998.tb00171.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/39057"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-72-3-595"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.4.2096-2101.1992"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5295.2079"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.48.32230"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/2654"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.7.2839"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410390613"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/383685a0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/386232a0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199908)46:2<224::AID-ANA12>3.0.CO;2-W"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/352340a0"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1439789"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)93128-V"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.1994.0034"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410380107"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.61.12.3688-3693.1987"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.32.19173"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(87)90380-8"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0997-1009"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.21.9690"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1986.5.315"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.14.8322"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(84)90533-6"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/9030"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0196-59"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/35014735"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.97.18.10168","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T17:30:40Z","timestamp":1649871040000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.97.18.10168"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,8,29]]},"references-count":29,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2000,8,29]]}},"alternative-id":["10.1073\/pnas.97.18.10168"],"URL":"https:\/\/doi.org\/10.1073\/pnas.97.18.10168","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,8,29]]},"assertion":[{"value":"2000-04-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-06-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-08-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}