In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 94, No. 19 ( 1997-09-16), p. 10086-10091
Kurzfassung:
The scrapie prion protein (PrP Sc ) is the major, and possibly the only, component of the infectious prion; it is generated from the cellular isoform (PrP C ) by a conformational change. N-terminal truncation of PrP Sc by limited proteolysis produces a protein of ≈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 α-helical form resembling PrP C , 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 β-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 PrP Sc 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 PrP C into PrP Sc , whereas the discontinuous epitope near the C terminus controls this transition.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.94.19.10086
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
1997
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12
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