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Prion recognition elements govern nucleation, strain specificity and species barriers

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  • Peter M. Tessier

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Susan Lindquist

    (Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA)

Abstract

Prions are proteins that can switch to self-perpetuating, infectious conformations. The abilities of prions to replicate, form structurally distinct strains, and establish and overcome transmission barriers between species are poorly understood. We exploit surface-bound peptides to overcome complexities of investigating such problems in solution. For the yeast prion Sup35, we find that the switch to the prion state is controlled with exquisite specificity by small elements of primary sequence. Strikingly, these same sequence elements govern the formation of distinct self-perpetuating conformations (prion strains) and determine species-specific seeding activities. A Sup35 chimaera that traverses the transmission barrier between two yeast species possesses the critical sequence elements from both. Using this chimaera, we show that the influence of environment and mutations on the formation of species-specific strains is driven by selective recognition of either sequence element. Thus, critical aspects of prion conversion are enciphered by subtle differences between small, highly specific recognition elements.

Suggested Citation

  • Peter M. Tessier & Susan Lindquist, 2007. "Prion recognition elements govern nucleation, strain specificity and species barriers," Nature, Nature, vol. 447(7144), pages 556-561, May.
    • Handle: RePEc:nat:nature:v:447:y:2007:i:7144:d:10.1038_nature05848
    DOI: 10.1038/nature05848
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    Cited by:

    1. Allen W Bryan Jr. & Matthew Menke & Lenore J Cowen & Susan L Lindquist & Bonnie Berger, 2009. "BETASCAN: Probable β-amyloids Identified by Pairwise Probabilistic Analysis," PLOS Computational Biology, Public Library of Science, vol. 5(3), pages 1-11, March.

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