CRYSTAL STRUCTURE OF THE GLOBULAR REGION OF THE PRION PROTIEN URE2 FROM YEAST SACCHAROMYCES CEREVISIAE

File:1g6y.jpg


PDB ID 1g6y

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, resolution 2.8Å
Gene: URE2 OR YNL229C OR N1165 (Saccharomyces cerevisiae)
Coordinates: save as pdb, mmCIF, xml



OverviewOverview

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.

About this StructureAbout this Structure

1G6Y is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.

ReferenceReference

Structure of the globular region of the prion protein Ure2 from the yeast Saccharomyces cerevisiae., Bousset L, Belrhali H, Janin J, Melki R, Morera S, Structure. 2001 Jan 10;9(1):39-46. PMID:11342133

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