YEAST 2017

28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

August 27 – September 1, 2017
Prague, Czech Republic

Paper ID: 293

Anti-Prion Systems in S. cerevisiae

Wickner Reed

Laboratory of Biochemistry & Genetics, NIDDK, NIH (USA)


[URE3] and [PSI+] are amyloid-based prions of Ure2p and Sup35p, respectively. The infectious amyloid filaments of Ure2p and Sup35p each have an in-register parallel β-sheet architecture, with the β-sheets folded along the long axis of the filaments. This architecture naturally suggests a conformational templating mechanism, explaining how these proteins can act as genes (Wickner RB, et al. Microbiol Mol Biol Rev 79: 1-17 (2015)).

Overproduction of Btn2p or Cur1p cures any [URE3] prion variant, and at normal levels cures most prions arising in their absence. They thus constitute an anti-prion system protecting the cells from the known detrimental effects of all [URE3] variants. Btn2p curing occurs by collecting the Ure2p amyloid aggregates at one place in the cell, resulting in frequent prion - free daughter cells (Kryndushkin et al. EMBO J 27: 2725 (2008); Wickner et al. PNAS 2014 pnas.1409582111). Normal-level Btn2p curing works on variants with lower seed number than those whose curing requires overproduction of Btn2p. The disaggregating chaperone Hsp104 is needed by most yeast amyloid-based prions to generate new seeds, but overproduction of Hsp104 cures any [PSI+] variant. Mutations in the N-terminus of Hsp104, such as T160M, eliminate the overproduction - curing function of Hsp104, without affecting its prion promoting activity. We found that most [PSI+] variants arising in an hsp104T160M strain are eliminated by restoration of just normal levels of the normal protein (Gorkovskiy and Wickner, PNAS, 2017 pnas.1704016114). Thus, like Btn2p and Cur1p action on [URE3], Hsp104 is an anti-prion system working on the generally detrimental and sometimes lethal [PSI+] prion.

We have carried out a general screen for anti-prion systems working on [PSI+] demanding that they work without overexpression, using an approach similar to that developed for Btn2, Cur1 and Hsp104.  

prion, amyloid, templating protein conformation, Btn2, Cur1, Hsp104, anti-prion, in-register parallel, beta sheet
Presented as:
  KL2 Keynote lecture 2 in Keynote Lectures

Institute of Microbiology

YEAST 2017
28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

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