{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:36:02Z","timestamp":1781105762879,"version":"3.54.1"},"reference-count":44,"publisher":"National Academy of Sciences","issue":"6","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,3,13]]},"abstract":"<jats:p>\n                    Under certain conditions, the prion protein (PrP) undergoes a\n conformational change from the normal cellular isoform,\n PrP\n                    <jats:sup>C<\/jats:sup>\n                    , to PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    , an infectious isoform capable\n of causing neurodegenerative diseases in many mammals. Conversion can\n be triggered by low pH, and\n                    <jats:italic>in vivo<\/jats:italic>\n                    this appears to\n take place in an endocytic pathway and\/or caveolae-like domains. It\n has thus far been impossible to characterize the conformational change\n at high resolution by experimental methods. Therefore, to investigate\n the effect of acidic pH on PrP conformation, we have performed 10-ns\n molecular dynamics simulations of PrP\n                    <jats:sup>C<\/jats:sup>\n                    in water at neutral\n and low pH. The core of the protein is well maintained at neutral pH.\n At low pH, however, the protein is more dynamic, and the\n sheet-like structure increases both by lengthening of the native\n \u03b2-sheet and by addition of a portion of the N terminus to widen the\n sheet by another two strands. The side chain of Met-129, a\n polymorphic codon in humans associated with variant Creutzfeldt\u2013Jakob\n disease, pulls the N terminus into the sheet. Neutralization of Asp-178\n at low pH removes interactions that inhibit conversion, which is\n consistent with the Asp-178\u2013Asn mutation causing human prion diseases.\n                  <\/jats:p>","DOI":"10.1073\/pnas.061555898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"2985-2989","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":145,"title":["Mapping the early steps in the pH-induced conformational conversion of the prion protein"],"prefix":"10.1073","volume":"98","author":[{"given":"Darwin O. V.","family":"Alonso","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, University of Washington,\r Seattle, WA 98195-7610; and Departments of Pathology\r (Neuropathology), and Molecular and Cellular\r Pharmacology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"DeArmond","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Washington,\r Seattle, WA 98195-7610; and Departments of Pathology\r (Neuropathology), and Molecular and Cellular\r Pharmacology, University of California, San Francisco, CA 94143"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred E.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Washington,\r Seattle, WA 98195-7610; and Departments of Pathology\r (Neuropathology), and Molecular and Cellular\r Pharmacology, University of 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