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Science 26 February 1999:
Vol. 283. no. 5406, pp. 1339 - 1343
DOI: 10.1126/science.283.5406.1339
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Reports

Prion Domain Initiation of Amyloid Formation in Vitro from Native Ure2p

Kimberly L. Taylor, 1 Naiqian Cheng, 2 Robert W. Williams, 3 Alasdair C. Steven, 2 Reed B. Wickner 1*

The [URE3] non-Mendelian genetic element of Saccharomyces cerevisiae is an infectious protein (prion) form of Ure2p, a regulator of nitrogen catabolism. Here, synthetic Ure2p1-65 were shown to polymerize to form filaments 40 to 45 angstroms in diameter with more than 60 percent beta  sheet. Ure2p1-65 specifically induced full-length native Ure2p to copolymerize under conditions where native Ure2p alone did not polymerize. Like Ure2p in extracts of [URE3] strains, these 180- to 220-angstrom-diameter filaments were protease resistant. The Ure2p1-65-Ure2p cofilaments could seed polymerization of native Ure2p to form thicker, less regular filaments. All filaments stained with Congo Red to produce the green birefringence typical of amyloid. This self-propagating amyloid formation can explain the properties of [URE3].

1  Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0830, USA.
2 Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-2717, USA.
3 Department of Biochemistry and Molecular Biology, Uniformed Services University for Health Sciences, Bethesda, MD 20814, USA.
*   To whom correspondence should be addressed. E-mail: wickner{at}helix.nih.gov

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J. Cell Biol. 153, 1327-1336
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[URE3] Prion Propagation in Saccharomyces cerevisiae: Requirement for Chaperone Hsp104 and Curing by Overexpressed Chaperone Ydj1p.
H. Moriyama, H. K. Edskes, and R. B. Wickner (2000)
Mol. Cell. Biol. 20, 8916-8922
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Prions in Saccharomyces and Podospora spp.: Protein-Based Inheritance.
R. B. Wickner, K. L. Taylor, H. K. Edskes, M.-L. Maddelein, H. Moriyama, and B. T. Roberts (1999)
Microbiol. Mol. Biol. Rev. 63, 844-861
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Mutational Analysis of the [Het-s] Prion Analog of Podospora anserina: A Short N-Terminal Peptide Allows Prion Propagation.
V. Coustou, C. Deleu, S. J. Saupe, and J. Bégueret (1999)
Genetics 153, 1629-1640
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Mks1p Is a Regulator of Nitrogen Catabolism Upstream of Ure2p in Saccharomyces cerevisiae.
H. K. Edskes, J. A. Hanover, and R. B. Wickner (1999)
Genetics 153, 585-594
   Abstract »    Full Text »    PDF »
Celebrating Similarities---Embracing Differences.
L. Goodman (1999)
Genome Res. 9, 797-800
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Genetic Study of Interactions Between the Cytoskeletal Assembly Protein Sla1 and Prion-Forming Domain of the Release Factor Sup35 (eRF3) in Saccharomyces cerevisiae.
P. A. Bailleul, G. P. Newnam, J. N. Steenbergen, and Y. O. Chernoff (1999)
Genetics 153, 81-94
   Abstract »    Full Text »
Two Prion-Inducing Regions of Ure2p Are Nonoverlapping.
M.-L. Maddelein and R. B. Wickner (1999)
Mol. Cell. Biol. 19, 4516-4524
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Strong Growth Polarity of Yeast Prion Fiber Revealed by Single Fiber Imaging.
Y. Inoue, A. Kishimoto, J. Hirao, M. Yoshida, and H. Taguchi (2001)
J. Biol. Chem. 276, 35227-35230
   Abstract »    Full Text »    PDF »
Tripartite Regulation of Gln3p by TOR, Ure2p, and Phosphatases.
P. G. Bertram, J. H. Choi, J. Carvalho, W. Ai, C. Zeng, T.-F. Chan, and X. F. S. Zheng (2000)
J. Biol. Chem. 275, 35727-35733
   Abstract »    Full Text »    PDF »
The crystal structure of the nitrogen regulation fragment of the yeast prion protein Ure2p.
T. C. Umland, K. L. Taylor, S. Rhee, R. B. Wickner, and D. R. Davies (2001)
PNAS 98, 1459-1464
   Abstract »    Full Text »    PDF »
A protein required for prion generation: [URE3] induction requires the Ras-regulated Mks1 protein.
H. K. Edskes and R. B. Wickner (2000)
PNAS 97, 6625-6629
   Abstract »    Full Text »    PDF »
A novel Rtg2p activity regulates nitrogen catabolism in yeast.
M. M. Pierce, M.-L. Maddelein, B. T. Roberts, and R. B. Wickner (2001)
PNAS 98, 13213-13218
   Abstract »    Full Text »    PDF »
RTG-dependent Mitochondria-to-Nucleus Signaling Is Regulated by MKS1 and Is Linked to Formation of Yeast Prion [URE3].
T. Sekito, Z. Liu, J. Thornton, and R. A. Butow (2002)
Mol. Biol. Cell 13, 795-804
   Abstract »    Full Text »    PDF »


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