PDBsum entry 1g6y

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Structural genomics PDB id
Protein chains
245 a.a. *
Waters ×21
* Residue conservation analysis
PDB id:
Name: Structural genomics
Title: Crystal structure of the globular region of the prion protien ure2 from yeast saccharomyces cerevisiae
Structure: Ure2 protein. Chain: a, b. Fragment: globular domain (residues 94-354). Synonym: ure2p. Engineered: yes
Source: Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Gene: ure2 or ynl229c or n1165. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
2.80Å     R-factor:   0.218     R-free:   0.293
Authors: L.Bousset,H.Belrhali,J.Janin,R.Melki,S.Morera
Key ref:
L.Bousset et al. (2001). Structure of the globular region of the prion protein Ure2 from the yeast Saccharomyces cerevisiae. Structure, 9, 39-46. PubMed id: 11342133 DOI: 10.1016/S0969-2126(00)00553-0
08-Nov-00     Release date:   21-Feb-01    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P23202  (URE2_YEAST) -  Transcriptional regulator URE2
354 a.a.
245 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Glutathione peroxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 glutathione + H2O2 = glutathione disulfide + 2 H2O
2 × glutathione
+ H(2)O(2)
= glutathione disulfide
+ 2 × H(2)O
      Cofactor: Se(2+)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     regulation of nitrogen utilization   1 term 
  Biochemical function     transcription corepressor activity     1 term  


DOI no: 10.1016/S0969-2126(00)00553-0 Structure 9:39-46 (2001)
PubMed id: 11342133  
Structure of the globular region of the prion protein Ure2 from the yeast Saccharomyces cerevisiae.
L.Bousset, H.Belrhali, J.Janin, R.Melki, S.Morera.
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.
  Selected figure(s)  
Figure 3.
Figure 3. Stereo View of the Ure2p 95-354 DimerThe two monomers are differently colored. The central b sheet is in red. The 2-fold axis is in the plane of the drawing in (a), and orthogonal to it in (b)

  The above figure is reprinted by permission from Cell Press: Structure (2001, 9, 39-46) copyright 2001.  
  Figure was selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21428697 A.Oakley (2011).
Glutathione transferases: a structural perspective.
  Drug Metab Rev, 43, 138-151.  
21219467 U.Baxa, P.W.Keller, N.Cheng, J.S.Wall, and A.C.Steven (2011).
In Sup35p filaments (the [PSI+] prion), the globular C-terminal domains are widely offset from the amyloid fibril backbone.
  Mol Microbiol, 79, 523-532.  
21419850 Y.Q.Wang, M.Bongiovanni, S.L.Gras, and S.Perrett (2011).
The fibrils of Ure2p homologs from Saccharomyces cerevisiae and Saccharoymyces paradoxus have similar cross-β structure in both dried and hydrated forms.
  J Struct Biol, 174, 505-511.  
21091436 Y.Yu, H.Y.Wang, M.Bai, and S.Perrett (2011).
Flexibility of the Ure2 prion domain is important for amyloid fibril formation.
  Biochem J, 434, 143-151.  
  20824085 C.Zhang, A.P.Jackson, Z.R.Zhang, Y.Han, S.Yu, R.Q.He, and S.Perrett (2010).
Amyloid-like aggregates of the yeast prion protein ure2 enter vertebrate cells by specific endocytotic pathways and induce apoptosis.
  PLoS One, 5, 0.  
20740275 T.T.Todorova, A.V.Kujumdzieva, and S.Vuilleumier (2010).
Non-enzymatic roles for the URE2 glutathione S-transferase in the response of Saccharomyces cerevisiae to arsenic.
  Arch Microbiol, 192, 909-918.  
21078122 V.Redeker, J.Bonnefoy, J.P.Le Caer, S.Pemberton, O.Laprévote, and R.Melki (2010).
A region within the C-terminal domain of Ure2p is shown to interact with the molecular chaperone Ssa1p by the use of cross-linkers and mass spectrometry.
  FEBS J, 277, 5112-5123.  
19861427 L.C.Reineke, and W.C.Merrick (2009).
Characterization of the functional role of nucleotides within the URE2 IRES element and the requirements for eIF2A-mediated repression.
  RNA, 15, 2264-2277.  
19258323 L.Fei, and S.Perrett (2009).
Disulfide Bond Formation Significantly Accelerates the Assembly of Ure2p Fibrils because of the Proximity of a Potential Amyloid Stretch.
  J Biol Chem, 284, 11134-11141.  
19383475 L.Pieri, M.Bucciantini, P.Guasti, J.Savistchenko, R.Melki, and M.Stefani (2009).
Synthetic lipid vesicles recruit native-like aggregates and affect the aggregation process of the prion Ure2p: insights on vesicle permeabilization and charge selectivity.
  Biophys J, 96, 3319-3330.  
19321443 Z.R.Zhang, and S.Perrett (2009).
Novel Glutaredoxin Activity of the Yeast Prion Protein Ure2 Reveals a Native-like Dimer within Fibrils.
  J Biol Chem, 284, 14058-14067.  
18400756 J.Savistchenko, J.Krzewska, N.Fay, and R.Melki (2008).
Molecular chaperones and the assembly of the prion Ure2p in vitro.
  J Biol Chem, 283, 15732-15739.  
18441120 K.H.Wong, M.J.Hynes, and M.A.Davis (2008).
Recent advances in nitrogen regulation: a comparison between Saccharomyces cerevisiae and filamentous fungi.
  Eukaryot Cell, 7, 917-925.  
17324933 H.Y.Lian, H.Zhang, Z.R.Zhang, H.M.Loovers, G.W.Jones, P.J.Rowling, L.S.Itzhaki, J.M.Zhou, and S.Perrett (2007).
Hsp40 interacts directly with the native state of the yeast prion protein Ure2 and inhibits formation of amyloid-like fibrils.
  J Biol Chem, 282, 11931-11940.  
16571726 L.Pieri, M.Bucciantini, D.Nosi, L.Formigli, J.Savistchenko, R.Melki, and M.Stefani (2006).
The yeast prion Ure2p native-like assemblies are toxic to mammalian cells regardless of their aggregation state.
  J Biol Chem, 281, 15337-15344.  
17001037 N.Ranson, T.Stromer, L.Bousset, R.Melki, and L.C.Serpell (2006).
Insights into the architecture of the Ure2p yeast protein assemblies from helical twisted fibrils.
  Protein Sci, 15, 2481-2487.  
16353200 S.Osváth, M.Jäckel, G.Agócs, P.Závodszky, G.Köhler, and J.Fidy (2006).
Domain interactions direct misfolding and amyloid formation of yeast phosphoglycerate kinase.
  Proteins, 62, 909-917.  
16131495 N.Fay, V.Redeker, J.Savistchenko, S.Dubois, L.Bousset, and R.Melki (2005).
Structure of the prion Ure2p in protein fibrils assembled in vitro.
  J Biol Chem, 280, 37149-37158.  
15956663 N.Talarek, L.Maillet, C.Cullin, and M.Aigle (2005).
The [URE3] prion is not conserved among Saccharomyces species.
  Genetics, 171, 23-34.  
16207084 S.Catharino, J.Buchner, and S.Walter (2005).
Characterization of oligomeric species in the fibrillization pathway of the yeast prion Ure2p.
  Biol Chem, 386, 633-641.  
15621414 S.McGoldrick, S.M.O'Sullivan, and D.Sheehan (2005).
Glutathione transferase-like proteins encoded in genomes of yeasts and fungi: insights into evolution of a multifunctional protein superfamily.
  FEMS Microbiol Lett, 242, 1.  
15282319 E.D.Ross, U.Baxa, and R.B.Wickner (2004).
Scrambled prion domains form prions and amyloid.
  Mol Cell Biol, 24, 7206-7213.  
15456789 L.Ripaud, L.Maillet, F.Immel-Torterotot, F.Durand, and C.Cullin (2004).
The [URE3] yeast prion results from protein aggregates that differ from amyloid filaments formed in vitro.
  J Biol Chem, 279, 50962-50968.  
15371425 M.Bai, J.M.Zhou, and S.Perrett (2004).
The yeast prion protein Ure2 shows glutathione peroxidase activity in both native and fibrillar forms.
  J Biol Chem, 279, 50025-50030.  
16117685 R.B.Wickner, H.K.Edskes, E.D.Ross, M.M.Pierce, F.Shewmaker, U.Baxa, and A.Brachmann (2004).
Prions of yeast are genes made of protein: amyloids and enzymes.
  Cold Spring Harb Symp Quant Biol, 69, 489-496.  
15355224 R.B.Wickner, H.K.Edskes, E.D.Ross, M.M.Pierce, U.Baxa, A.Brachmann, and F.Shewmaker (2004).
Prion genetics: new rules for a new kind of gene.
  Annu Rev Genet, 38, 681-707.  
12925776 A.Baudin-Baillieu, E.Fernandez-Bellot, F.Reine, E.Coissac, and C.Cullin (2003).
Conservation of the prion properties of Ure2p through evolution.
  Mol Biol Cell, 14, 3449-3458.  
12777380 N.Fay, Y.Inoue, L.Bousset, H.Taguchi, and R.Melki (2003).
Assembly of the yeast prion Ure2p into protein fibrils. Thermodynamic and kinetic characterization.
  J Biol Chem, 278, 30199-30205.  
12562760 R.Rai, J.J.Tate, and T.G.Cooper (2003).
Ure2, a prion precursor with homology to glutathione S-transferase, protects Saccharomyces cerevisiae cells from heavy metal ion and oxidant toxicity.
  J Biol Chem, 278, 12826-12833.  
12917441 U.Baxa, K.L.Taylor, J.S.Wall, M.N.Simon, N.Cheng, R.B.Wickner, and A.C.Steven (2003).
Architecture of Ure2p prion filaments: the N-terminal domains form a central core fiber.
  J Biol Chem, 278, 43717-43727.  
12177423 H.K.Edskes, and R.B.Wickner (2002).
Conservation of a portion of the S. cerevisiae Ure2p prion domain that interacts with the full-length protein.
  Proc Natl Acad Sci U S A, 99, 16384-16391.  
12065404 L.Bousset, N.H.Thomson, S.E.Radford, and R.Melki (2002).
The yeast prion Ure2p retains its native alpha-helical conformation upon assembly into protein fibrils in vitro.
  EMBO J, 21, 2903-2911.  
11916832 P.Tompa, G.E.Tusnády, P.Friedrich, and I.Simon (2002).
The role of dimerization in prion replication.
  Biophys J, 82, 1711-1718.  
12142498 S.M.Uptain, and S.Lindquist (2002).
Prions as protein-based genetic elements.
  Annu Rev Microbiol, 56, 703-741.  
11959975 U.Baxa, V.Speransky, A.C.Steven, and R.B.Wickner (2002).
Mechanism of inactivation on prion conversion of the Saccharomyces cerevisiae Ure2 protein.
  Proc Natl Acad Sci U S A, 99, 5253-5260.  
11685241 S.Dietmann, and L.Holm (2001).
Identification of homology in protein structure classification.
  Nat Struct Biol, 8, 953-957.  
11171973 T.C.Umland, K.L.Taylor, S.Rhee, R.B.Wickner, and D.R.Davies (2001).
The crystal structure of the nitrogen regulation fragment of the yeast prion protein Ure2p.
  Proc Natl Acad Sci U S A, 98, 1459-1464.
PDB code: 1hqo
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.