{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:31:04Z","timestamp":1793334664043,"version":"4.5.0"},"reference-count":24,"publisher":"National Academy of Sciences","issue":"15","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,7,17]]},"abstract":"<jats:p>\n                    Although a functional role in copper binding has been suggested for the prion protein, evidence for binding at affinities characteristic of authentic metal-binding proteins has been lacking. By presentation of copper(II) ions in the presence of the weak chelator glycine, we have now characterized two high-affinity binding sites for divalent transition metals within the human prion protein. One is in the N-terminal octapeptide-repeat segment and has a\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    for copper(II) of 10\n                    <jats:sup>\u221214<\/jats:sup>\n                    M, with other metals (Ni\n                    <jats:sup>2+<\/jats:sup>\n                    , Zn\n                    <jats:sup>2+<\/jats:sup>\n                    , and Mn\n                    <jats:sup>2+<\/jats:sup>\n                    ) binding three or more orders of magnitude more weakly. However, NMR and fluorescence data reveal a previously unreported second site around histidines 96 and 111, a region of the molecule known to be crucial for prion propagation. The\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>d<\/jats:sub>\n                    for copper(II) at this site is 4 \u00d7 10\n                    <jats:sup>\u221214<\/jats:sup>\n                    M, whereas nickel(II), zinc(II), and manganese(II) bind 6, 7, and 10 orders of magnitude more weakly, respectively, regardless of whether the protein is in its oxidized \u03b1-helical (\u03b1-PrP) or reduced \u03b2-sheet (\u03b2-PrP) conformation. A role for prion protein (PrP) in copper metabolism or transport seems likely and disturbance of this function may be involved in prion-related neurotoxicity.\n                  <\/jats:p>","DOI":"10.1073\/pnas.151038498","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:37:36Z","timestamp":1027679856000},"page":"8531-8535","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":417,"title":["Location and properties of metal-binding sites on the human prion protein"],"prefix":"10.1073","volume":"98","author":[{"given":"Graham S.","family":"Jackson","sequence":"first","affiliation":[{"name":"Medical Research Council Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1NY, United Kingdom; Krebs Institute for Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom; and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Murray","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1NY, United Kingdom; Krebs Institute for Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom; and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laszlo L. P.","family":"Hosszu","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1NY, United Kingdom; Krebs Institute for Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom; and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Gibbs","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1NY, United Kingdom; Krebs Institute for Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom; and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan P.","family":"Waltho","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1NY, United Kingdom; Krebs Institute for Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom; and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony R.","family":"Clarke","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1NY, United Kingdom; Krebs Institute for Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom; and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[{"name":"Medical Research Council Prion Unit, Department of Neurogenetics, Imperial College School of Medicine at St. Mary's, London W2 1NY, United Kingdom; Krebs Institute for Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, United Kingdom; and Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2001,7,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13363"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-440X(99)00051-2"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00059a016"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.23.10962"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/9030"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/230115a0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/37783"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.11.7455"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj3440001"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.50.33107"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1233"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.2384"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi972827k"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.2042"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1110\/ps.9.2.332"},{"key":"e_1_3_3_16_2","first-page":"399","volume-title":"Data for Biochemical Research","author":"Dawson R M C","year":"1986","unstructured":", eds R M C Dawson, D Elliot, W Elliot, K M Jones (Clarendon, Oxford) Data for Biochemical Research, pp. 399\u2013415 (1986)."},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5409.1935"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/11507"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01874573"},{"key":"e_1_3_3_20_2","first-page":"207","volume":"98","author":"Davis A L","year":"1992","unstructured":"A L Davis, J Keeler, E D Laue, D J Moskau J Magn Reson Ser B 98, 207\u2013216 (1992).","journal-title":"J Magn Reson Ser B"},{"key":"e_1_3_3_21_2","unstructured":"Gibbs N. 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