Immobilized prion protein undergoes spontaneous rearrangement to a conformation having features in common with the infectious form

Estelle Leclerc, David Peretz, Haydn Ball, Hiroshi Sakurai, Giuseppe Legname, Ana Serban, Stanley B. Prusiner, Dennis R. Burton, R. Anthony Williamson

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

It is hypothesized that infectious prions are generated as the cellular form of the prion protein (PrPC) undergoes pronounced conformational change under the direction of an infectious PrPSc 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 PrPc 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.

Original languageEnglish (US)
Pages (from-to)1547-1554
Number of pages8
JournalEMBO Journal
Volume20
Issue number7
DOIs
StatePublished - Apr 2 2001

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Immobilized Proteins
Prions
PrPC Proteins
Conformations
Flexible structures
Protein Isoforms
Proteins
Molecules
Antibodies
Prion Proteins
Direction compound

Keywords

  • Conformational change
  • Phage display
  • Prion protein
  • Recombinant antibodies

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Immobilized prion protein undergoes spontaneous rearrangement to a conformation having features in common with the infectious form. / Leclerc, Estelle; Peretz, David; Ball, Haydn; Sakurai, Hiroshi; Legname, Giuseppe; Serban, Ana; Prusiner, Stanley B.; Burton, Dennis R.; Williamson, R. Anthony.

In: EMBO Journal, Vol. 20, No. 7, 02.04.2001, p. 1547-1554.

Research output: Contribution to journalArticle

Leclerc, E, Peretz, D, Ball, H, Sakurai, H, Legname, G, Serban, A, Prusiner, SB, Burton, DR & Williamson, RA 2001, 'Immobilized prion protein undergoes spontaneous rearrangement to a conformation having features in common with the infectious form', EMBO Journal, vol. 20, no. 7, pp. 1547-1554. https://doi.org/10.1093/emboj/20.7.1547
Leclerc, Estelle ; Peretz, David ; Ball, Haydn ; Sakurai, Hiroshi ; Legname, Giuseppe ; Serban, Ana ; Prusiner, Stanley B. ; Burton, Dennis R. ; Williamson, R. Anthony. / Immobilized prion protein undergoes spontaneous rearrangement to a conformation having features in common with the infectious form. In: EMBO Journal. 2001 ; Vol. 20, No. 7. pp. 1547-1554.
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