title: Structure of the globular region of the prion protein Ure2 from the yeast Saccharomyces cerevisiae.
abstract: BACKGROUND
  The [URE3] non-Mendelian element of the yeast S. cerevisiae is due to the propagation of a transmissible form of the protein Ure2. The infectivity of Ure2p is thought to originate from a conformational change of the normal form of the prion protein. This conformational change generates a form of Ure2p that assembles into amyloid fibrils. Hence, knowledge of the three-dimensional structure of prion proteins such as Ure2p should help in understanding the mechanism of amyloid formation associated with a number of neurodegenerative diseases.
  
  
  RESULTS
  Here we report the three-dimensional crystal structure of the globular region of Ure2p (residues 95--354), also called the functional region, solved at 2.5 A resolution by the MAD method. The structure of Ure2p 95--354 shows a two-domain protein forming a globular dimer. The N-terminal domain is composed of a central 4 strand beta sheet flanked by four alpha helices, two on each side. In contrast, the C-terminal domain is entirely alpha-helical. The fold of Ure2p 95--354 resembles that of the beta class glutathione S-transferases (GST), in line with a weak similarity in the amino acid sequence that exists between these proteins. Ure2p dimerizes as GST does and possesses a potential ligand binding site, although it lacks GST activity.
  
  
  CONCLUSIONS
  The structure of the functional region of Ure2p is the first crystal structure of a prion protein. Structure comparisons between Ure2p 95--354 and GST identified a 32 amino acid residues cap region in Ure2p exposed to the solvent. The cap region is highly flexible and may interact with the N-terminal region of the partner subunit in the dimer. The implication of this interaction in the assembly of Ure2p into amyloid fibrils is discussed.
authors.affiliation: Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: L
authors.initials: L
authors.lastname: Bousset
authors.forename: H
authors.initials: H
authors.lastname: Belrhali
authors.forename: J
authors.initials: J
authors.lastname: Janin
authors.forename: R
authors.initials: R
authors.lastname: Melki
authors.forename: S
authors.initials: S
authors.lastname: Morera
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry*; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid
chemical_list: D000682:Amyloid; D005656:Fungal Proteins; D008024:Ligands; D011328:Prions; D029701:Saccharomyces cerevisiae Proteins; D005979:Glutathione Peroxidase; C067020:URE2 protein, S cerevisiae; D005982:Glutathione Transferase