The crystal structure of the nitrogen regulation fragment of the yeast prion protein Ure2p.
The yeast nonchromosomal gene [URE3] is due to a prion form of the nitrogen regulatory protein Ure2p. It is a negative regulator of nitrogen catabolism and acts by inhibiting the transcription factor Gln3p. Ure2p residues 1--80 are necessary for prion generation and propagation. The C-terminal fragment retains nitrogen regulatory activity, albeit somewhat less efficiently than the full-length protein, and it also lowers the frequency of prion generation. The crystal structure of this C-terminal fragment, Ure2p(97--354), at 2.3 A resolution is described here. It adopts the same fold as the glutathione S-transferase superfamily, consistent with their sequence similarity. However, Ure2p(97--354) lacks a properly positioned catalytic residue that is required for S-transferase activity. Residues within this regulatory fragment that have been indicated by mutational studies to influence prion generation have been mapped onto the three-dimensional structure, and possible implications for prion activity are discussed.
Umland
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TC
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0560, USA.
Taylor
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KL
Rhee
S
S
Wickner
R B
RB
Davies
D R
DR
D000595:Amino Acid Sequence; D018360:Crystallography, X-Ray; D005656:Fungal Proteins / Q000737:chemistry* / Q000235:genetics; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009584:Nitrogen / Q000378:metabolism*; D011328:Prions; D017433:Protein Structure, Secondary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins
D005656:Fungal Proteins; D011328:Prions; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae; D005982:Glutathione Transferase; D009584:Nitrogen