A G-protein γ subunit mimic is a general antagonist of prion propagation in Saccharomyces cerevisiae

Masao Ishiwata, Hiroshi Kurahashi, Yoshikazu Nakamura

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


The Gpg1 protein is a Gγ subunit mimic implicated in the G-protein glucose-signaling pathway in Saccharomyces cerevisiae, and its function is largely unknown. Here we report that Gpg1 blocks the maintenance of [PSI +], an aggregated prion form of the translation termination factor Sup35. Although the GPG1 gene is normally not expressed, over-expression of GPG1 inhibits propagation of not only [PSI+] but also [PIN+], [URE3] prions, and the toxic polyglutamine aggregate in S. cerevisiae. Over-expression of Gpg1 does not affect expression and activity of Hsp104, a protein-remodeling factor required for prion propagation, showing that Gpg1 does not target Hsp104 directly. Nevertheless, prion elimination by Gpg1 is weakened by over-expression of Hsp104. Importantly, Gpg1 protein is prone to self-aggregate and transiently colocalized with Sup35NM-prion aggregates when expressed in [PSI+] cells. Genetic selection and characterization of loss-of-activity gpg1 mutations revealed that multiple mutations on the hydrophobic one-side surface of predicted α-helices of the Gpg1 protein hampered the activity. Prion elimination by Gpg1 is unaffected in the gpa2Δ and gpb1Δ strains lacking the supposed physiological G-protein partners of Gpg1. These findings suggest a general inhibitory interaction of the Gpg1 protein with other transmissible and nontransmissible amyloids, resulting in prion elimination. Assuming the ability of Gpg1 to form G-protein heterotrimeric complexes, Gpg1 is likely to play a versatile function of reversing the prion state and modulating the G-protein signaling pathway.

Original languageEnglish
Pages (from-to)791-796
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
Publication statusPublished - 2009 Jan 20
Externally publishedYes


  • Gpg1
  • Yeast prion
  • [PIN]
  • [PSI]
  • [URE3]

ASJC Scopus subject areas

  • General


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