A Critical Role for Amino-Terminal Glutamine/Asparagine Repeats in the Formation and Propagation of a Yeast Prion
نویسندگان
چکیده
The yeast [PSI+] factor propagates by a prion-like mechanism involving self-replicating Sup35p amyloids. We identified multiple Sup35p mutants that either are poorly recruited into, or cause curing of, wildtype amyloids in vivo. In vitro, these mutants showed markedly decreased rates of amyloid formation, strongly supporting the protein-only prion hypothesis. Kinetic analysis suggests that the prion state replicates by accelerating slow conformational changes rather than by providing stable nuclei. Strikingly, our mutations map exclusively within a short glutamine/asparagine-rich region of Sup35p, and all but one occur at polar residues. Even after replacement of this region with polyglutamine, Sup35p retains its ability to form amyloids. These and other considerations suggest similarities between the prion-like propagation of [PSI+] and polyglutamine-mediated pathogenesis of several neurodegenerative diseases.
منابع مشابه
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NATURE | VOL 410 | 8 MARCH 2001 | www.nature.com 227 12. DePace, A. H., Santoso, A., Hillner, P. & Weissman, J. S. A critical role for amino-terminal glutamine/ asparagine repeats in the formation and propagation of a yeast prion. Cell 93, 1241–1252 (1998). 13. Patino, M. M., Liu, J. J., Glover, J. R. & Lindquist, S. Support for the prion hypothesis for inheritance of a phenotypic trait in yeas...
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ورودعنوان ژورنال:
- Cell
دوره 93 شماره
صفحات -
تاریخ انتشار 1998