The Crystal Structure of the Nitrogen Regulation Fragment of the Yeast Prion Protein Ure2p

• Published in: Proceedings of the National Academy of Sciences - PNAS 2001-02, Vol.98 (4), p.1459-1464
• Main Authors: Umland, Timothy C., Taylor, Kimberly L., Rhee, Sangkee, Wickner, Reed B., Davies, David R.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Atoms; Biochemistry; Biological Sciences; Crystallography, X-Ray; Crystals; Dimers; Fungal Proteins - chemistry; Fungal Proteins - genetics; Glutathione Peroxidase; Glutathione Transferase - chemistry; Goods and services tax; Models, Molecular; Molecular Sequence Data; Monomers; Mutation; Nitrogen; Nitrogen - metabolism; Prions; Protein Structure, Secondary; Proteins; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - genetics; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Solvents; Ure2 protein; URE3 gene; Yeast; Yeasts
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.041607898

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 Å 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.