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Immobilized prion protein undergoes spontaneous rearrangement to a conformation having features in common with the infectious form
Author(s) -
Leclerc Estelle,
Peretz David,
Ball Haydn,
Sakurai Hiroshi,
Legname Giuseppe,
Serban Ana,
Prusiner Stanley B.,
Burton Dennis R.,
Williamson R.Anthony
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.7.1547
Subject(s) - biology , virology , bacterial protein , genetics , gene
It is hypothesized that infectious prions are generated as the cellular form of the prion protein (PrP C ) undergoes pronounced conformational change under the direction of an infectious PrP Sc template. Conversion to the infectious conformer is particularly associated with major structural rearrangement in the central portion of the protein (residues 90–120), which has an extended flexible structure in the PrP C isoform. Using a panel of recombinant antibodies reactive with different parts of PrP, we show that equivalent major structural rearrangements occur spontaneously in this region of PrP immobilized on a surface. In contrast, regions more towards the termini of the protein remain relatively unaltered. The rearrangements occur even under conditions where individual PrP molecules should not contact one another. The propensity of specific unstructured regions of PrP to spontaneously undergo large and potentially deleterious conformational changes may have important implications for prion biology.