Mechanism of cross-species prion transmission: An infectious conformation compatible with two highly divergent yeast prion proteins

Motomasa Tanaka, Peter Chien, Koji Yonekura, Jonathan S. Weissman

Research output: Contribution to journalArticlepeer-review

156 Citations (Scopus)

Abstract

Efficiency of interspecies prion transmission decreases as the primary structures of the infectious proteins diverge. Yet, a single prion protein can misfold into multiple infectious conformations, and such differences in "strain conformation" also alter infection specificity. Here, we explored the relationship between prion strains and species barriers by creating distinct synthetic prion forms of the yeast prion protein Sup35. We identified a strain conformation of Sup35 that allows transmission from the S. cerevisiae (Sc) Sup35 to the highly divergent C. albicans (Ca) Sup35 both in vivo and in vitro. Remarkably, cross-species transmission leads to a novel Ca strain that in turn can infect the Sc protein. Structural studies reveal strain-specific conformational differences in regions of the prion domain that are involved in intermolecular contacts. Our findings support a model whereby strain conformation is the critical determinant of cross-species prion transmission while primary structure affects transmission specificity by altering the spectrum of preferred amyloid conformations.

Original languageEnglish
Pages (from-to)49-62
Number of pages14
JournalCell
Volume121
Issue number1
DOIs
Publication statusPublished - 2005 Apr 8
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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