1b10: Difference between revisions
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'''SOLUTION NMR STRUCTURE OF RECOMBINANT SYRIAN HAMSTER PRION PROTEIN RPRP(90-231) , 25 STRUCTURES'''<br /> | '''SOLUTION NMR STRUCTURE OF RECOMBINANT SYRIAN HAMSTER PRION PROTEIN RPRP(90-231) , 25 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
The scrapie prion protein (PrPSc) is the major, and possibly the only, component of the infectious prion; it is generated from the cellular | 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 Structure== | ==About this Structure== | ||
1B10 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mesocricetus_auratus Mesocricetus auratus]. This structure | 1B10 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mesocricetus_auratus Mesocricetus auratus]. This structure supersedes the now removed PDB entry 2PRP. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1B10 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Farr-Jones, S.]] | [[Category: Farr-Jones, S.]] | ||
[[Category: James, T | [[Category: James, T L.]] | ||
[[Category: Liu, H.]] | [[Category: Liu, H.]] | ||
[[Category: Ulyanov, N | [[Category: Ulyanov, N B.]] | ||
[[Category: brain]] | [[Category: brain]] | ||
[[Category: glycoprotein]] | [[Category: glycoprotein]] | ||
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[[Category: scrapie]] | [[Category: scrapie]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:50:21 2008'' | ||
Revision as of 12:50, 21 February 2008
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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 supersedes 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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