{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:25:09Z","timestamp":1787790309877,"version":"build-2784847793"},"reference-count":23,"publisher":"National Academy of Sciences","issue":"28","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,7,13]]},"abstract":"<jats:p>\n                    Prion diseases are closely associated with the conversion of the cellular prion protein (PrP\n                    <jats:sup>C<\/jats:sup>\n                    ) to an abnormal conformer (PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    ) [Prusiner, S. B. (1998)\n                    <jats:italic>Proc. Natl. Acad. Sci. USA<\/jats:italic>\n                    95, 13363\u201313383]. Monoclonal antibodies that bind epitopes comprising residues 96\u2013104 and 133\u2013158 of PrP\n                    <jats:sup>C<\/jats:sup>\n                    potently inhibit this process, presumably by preventing heterodimeric association of PrP\n                    <jats:sup>C<\/jats:sup>\n                    and PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    , and suggest that these regions of PrP\n                    <jats:sup>C<\/jats:sup>\n                    may be critical components of the PrP\n                    <jats:sup>C<\/jats:sup>\n                    \u2013PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    replicative interface. We reasoned that transplanting PrP sequence corresponding to these regions into a suitable carrier molecule, such as an antibody, could impart specific recognition of disease-associated forms of PrP. To test this hypothesis, polypeptides containing PrP sequence between residues 89\u2013112 or 136\u2013158 were used to replace the extended heavy chain complementarity-determining region 3 of an IgG antibody specific for the envelope glycoprotein of HIV-1. Herein the resulting engineered PrP-IgGs are shown to bind specifically to infective fractions of PrP in mouse, human, and hamster prion-infected tissues, but not to PrP\n                    <jats:sup>C<\/jats:sup>\n                    , other cellular components, or the HIV-1 envelope. PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    reactivity was abolished when the sequence of the PrP 89\u2013112 and 136\u2013158 grafts was mutated, scrambled, or N-terminally truncated. Our findings suggest that residues within the 89\u2013112 and 136\u2013158 segments of PrP\n                    <jats:sup>C<\/jats:sup>\n                    are key components of one face of the PrP\n                    <jats:sup>C<\/jats:sup>\n                    \u2013PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    complex. PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    -specific antibodies produced by the approach described may find widespread application in the study of prion biology and replication and in the detection of infectious prions in human and animal materials.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0403522101","type":"journal-article","created":{"date-parts":[[2004,7,6]],"date-time":"2004-07-06T21:01:20Z","timestamp":1089147680000},"page":"10404-10409","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":104,"title":["Motif-grafted antibodies containing the replicative interface of cellular PrP are specific for PrP\n                    <sup>Sc<\/sup>"],"prefix":"10.1073","volume":"101","author":[{"given":"Gianluca","family":"Moroncini","sequence":"first","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nnennaya","family":"Kanu","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Solforosi","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Abalos","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glenn C.","family":"Telling","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Head","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Ironside","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy P.","family":"Brockes","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis R.","family":"Burton","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Anthony","family":"Williamson","sequence":"additional","affiliation":[{"name":"Departments of Immunology and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom; Sanders\u2013Brown Center on Aging, University of Kentucky, Lexington, KY 40536; and National Creutzfeldt\u2013Jakob Disease Surveillance Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,7,6]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13363"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/39057"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/38925"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/85423"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.19.10069"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.9.4351-4360.2000"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(01)01792-3"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/36337"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm883"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063093"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/35089090"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.11.9413-9418.1998"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151242598"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.21.13203"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.8.6245-6250.1999"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7973652"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.11.5214"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.7.6024-6030.1999"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/35044100"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061692"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.12.7754-7758.1995"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-77-11-2885"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2002.00995.x"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0403522101","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T09:53:45Z","timestamp":1649757225000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0403522101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7,6]]},"references-count":23,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2004,7,13]]}},"alternative-id":["10.1073\/pnas.0403522101"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0403522101","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,7,6]]},"assertion":[{"value":"2004-01-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-07-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}