1b10
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SOLUTION NMR STRUCTURE OF RECOMBINANT SYRIAN HAMSTER PRION PROTEIN RPRP(90-231) , 25 STRUCTURES
OverviewOverview
The scrapie prion protein (PrPSc) is the major, and possibly the only, component of the infectious prion; it is generated from the cellular, isoform (PrPC) by a conformational change. N-terminal truncation of PrPSc, by limited proteolysis produces a protein of approximately 142 residues, designated PrP 27-30, which retains infectivity. A recombinant protein, (rPrP) corresponding to Syrian hamster PrP 27-30 was expressed in, Escherichia coli and purified. After refolding rPrP into an alpha-helical, form resembling PrPC, the structure was solved by multidimensional, heteronuclear NMR, revealing many structural features of rPrP that were, not found in two shorter PrP fragments studied previously. Extensive, side-chain interactions for residues 113-125 characterize a hydrophobic, cluster, which packs against an irregular beta-sheet, whereas residues, 90-112 exhibit little defined structure. Although identifiable secondary, structure is largely lacking in the N terminus of rPrP, paradoxically this, N terminus increases the amount of secondary structure in the remainder of, rPrP. The surface of a long helix (residues 200-227) and a structured loop, (residues 165-171) form a discontinuous epitope for binding of a protein, that facilitates PrPSc formation. Polymorphic residues within this epitope, seem to modulate susceptibility of sheep and humans to prion disease., Conformational heterogeneity of rPrP at the N terminus may be key to the, transformation of PrPC into PrPSc, whereas the discontinuous epitope near, the C terminus controls this transition.
About this StructureAbout this Structure
1B10 is a Single protein structure of sequence from Mesocricetus auratus. This structure superseeds the now removed PDB entry 2PRP. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform., James TL, Liu H, Ulyanov NB, Farr-Jones S, Zhang H, Donne DG, Kaneko K, Groth D, Mehlhorn I, Prusiner SB, Cohen FE, Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10086-91. PMID:9294167
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