{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:07:19Z","timestamp":1791047239359,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"20","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,9,28]]},"abstract":"<jats:p>\n                    Prions are mammalian proteins (PrPs) with a unique pathogenic property: a nonendogenous isoform PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    can catalyze conversion of the endogenous PrP\n                    <jats:sup>C<\/jats:sup>\n                    isoform into additional PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    . In this work, we demonstrate that PrP\n                    <jats:sup>C<\/jats:sup>\n                    helix 1 has certain properties (hydrophilicity, charge distribution) that make it unique among all naturally occurring \u03b1-helices, and which are indicative of a highly specific model of prion infectivity. The \u03b2-nucleation model proposes that PrP\n                    <jats:sup>Sc<\/jats:sup>\n                    is an aggregate with a hydrophilic core, consisting of a \u03b2-sheet-like arrangement of constituent helix 1 components. It is suggested by using structural arguments, and confirmed by using\n                    <jats:sc>charmm<\/jats:sc>\n                    energy calculations, that aggregate formation from two PrP\n                    <jats:sup>C<\/jats:sup>\n                    molecules is highly unfavorable, but the addition of chains to an existing aggregate is favorable. The \u03b2-nucleation model is shown to be consistent with the prion species-barrier, as well as with infectivity data. Sequence analysis of all known protein structures indicates that PrP is uniquely suited to \u03b2-nucleation, in contrast to the many proteins that readily form less favorable (often nonspecific) hydrophobic aggregates.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.20.11293","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:38:21Z","timestamp":1027679901000},"page":"11293-11298","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":114,"title":["Evidence for the role of PrP\n                    <sup>C<\/sup>\n                    helix 1 in the hydrophilic seeding of prion aggregates"],"prefix":"10.1073","volume":"96","author":[{"given":"M. P.","family":"Morrissey","sequence":"first","affiliation":[{"name":"Division of Engineering and Applied Sciences, and Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. I.","family":"Shakhnovich","sequence":"additional","affiliation":[{"name":"Division of Engineering and Applied Sciences, and Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 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