1uw3
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THE CRYSTAL STRUCTURE OF THE GLOBULAR DOMAIN OF SHEEP PRION PROTEIN
OverviewOverview
The prion protein PrP is a naturally occurring polypeptide that becomes, transformed from a normal conformation to that of an aggregated form, characteristic of pathological states in fatal transmissible spongiform, conditions such as Creutzfeld-Jacob Disease and Bovine Spongiform, Encephalopathy. We report the crystal structure, at 2 A resolution, of, residues 123-230 of the C-terminal globular domain of the ARQ allele of, sheep prion protein (PrP). The asymmetric unit contains a single molecule, whose secondary structure and overall organisation correspond to those, structures of PrPs from various mammalian species determined by NMR. The, globular domain shows a close association of helix-1, the C-terminal, portion of helix-2 and the N-terminal portion of helix-3, bounded by the, intramolecular disulphide bond, 179-214. The loop 164-177, between beta2, and helix-2 is relatively well structured compared to the human PrP NMR, structure. Analysis of the sheep PrP structure identifies two possible, loci for the initiation of beta-sheet mediated polymerisation. One of, these comprises the beta-strand, residues 129-131 that forms an, intra-molecular beta-sheet with residues 161-163. This strand is involved, in lattice contacts about a crystal dyad to generate a four-stranded, intermolecular beta-sheet between neighbouring molecules. The second locus, involves the region 188-204, which modelling suggests is able to undergo a, partial alpha-->beta switch within the monomer. These loci provide sites, within the PrPc monomer that could readily give rise to early intermediate, species on the pathway to the formation of aggregated PrPSc containing, additional intermolecular beta-structure.
About this StructureAbout this Structure
1UW3 is a Single protein structure of sequence from Ovis aries with PO4 and GTT as ligands. Structure known Active Site: GTT. Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of the globular domain of sheep prion protein., Haire LF, Whyte SM, Vasisht N, Gill AC, Verma C, Dodson EJ, Dodson GG, Bayley PM, J Mol Biol. 2004 Mar 5;336(5):1175-83. PMID:15037077
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