A mutation within the C-terminal domain of Sup35p that affects [PSI(+) ] prion propagation. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Molecular Microbiology Année : 2011

A mutation within the C-terminal domain of Sup35p that affects [PSI(+) ] prion propagation.

Mehdi Kabani
Luc Bousset
Ronald Melki
  • Fonction : Auteur

Résumé

The epigenetic factor [PSI(+) ] in the yeast Saccharomyces cerevisiae is due to the prion form of Sup35p. The N-terminal domain of Sup35p (N), alone or together with the middle-domain (NM), assembles in vitro into fibrils that induce [PSI(+) ] when introduced into yeast cells. The Sup35p C-terminal domain (C), involved in translation termination, is essential for growth. The involvement of Sup35p C-terminal domain into [PSI(+) ] propagation is subject to debate. We previously showed that mutation of threonine 341 within Sup35p C-domain affects translation termination efficiency. Here, we demonstrate that mutating threonine 341 to aspartate or alanine results in synthetic lethality with [PSI(+) ] and weakening of [PSI(+) ], respectively. The corresponding Sup35D and Sup35A proteins assemble into wild-type like fibrils in vitro, but with a slower elongation rate. Moreover, cross-seeding between Sup35p and Sup35A is inefficient both in vivo and in vitro, suggesting that the point mutation alters the structural properties of Sup35p within the fibrils. Thus, Sup35p C-terminal domain modulates [PSI(+) ] prion propagation, possibly through a functional interaction with the N and/or M domains of the protein. Our results clearly demonstrate that Sup35p C-terminal domain plays a critical role in prion propagation and provide new insights into the mechanism of prion conversion.

Dates et versions

hal-00598328 , version 1 (06-06-2011)

Identifiants

Citer

Mehdi Kabani, Bruno Cosnier, Luc Bousset, Jean-Pierre Rousset, Ronald Melki, et al.. A mutation within the C-terminal domain of Sup35p that affects [PSI(+) ] prion propagation.. Molecular Microbiology, 2011, epub ahead of print. ⟨10.1111/j.1365-2958.2011.07719.x⟩. ⟨hal-00598328⟩
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