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Science 25 August 2000:
Vol. 289. no. 5483, pp. 1317 - 1321
DOI: 10.1126/science.289.5483.1317
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Research Articles

Nucleated Conformational Conversion and the Replication of Conformational Information by a Prion Determinant

Tricia R. Serio,1* Anil G. Cashikar,2* Anthony S. Kowal,2 George J. Sawicki,2 Jahan J. Moslehi,2 Louise Serpell,4 Morton F. Arnsdorf,3 Susan L. Lindquist12dagger

Prion proteins can serve as genetic elements by adopting distinct physical and functional states that are self-perpetuating and heritable. The critical region of one prion protein, Sup35, is initially unstructured in solution and then forms self-seeded amyloid fibers. We examined in vitro the mechanism by which this state is attained and replicated. Structurally fluid oligomeric complexes appear to be crucial intermediates in de novo amyloid nucleus formation. Rapid assembly ensues when these complexes conformationally convert upon association with nuclei. This model for replicating protein-based genetic information, nucleated conformational conversion, may be applicable to other protein assembly processes.

1 Department of Molecular Genetics and Cell Biology,
2 Howard Hughes Medical Institute,
3 Section of Cardiology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
4 Neurobiology Division, MRC Centre, Laboratory of Molecular Biology, Cambridge CB2 2QH, UK.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: s-lindquist{at}uchicago.edu

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Science. ISSN 0036-8075 (print), 1095-9203 (online)