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Mol Microbiol. 2011 Aug;81(3):640-58. doi: 10.1111/j.1365-2958.2011.07719.x. Epub 2011 Jun 16.

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

Author information

  • 1Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, Bât. 34, Avenue de la Terrasse, F-91190 Gif-sur-Yvette, France. mehdi.kabani@lebs.cnrs-gif.fr

Abstract

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.

© 2011 Blackwell Publishing Ltd.

PMID:
21631606
[PubMed - indexed for MEDLINE]
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