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.

Immobilized prion protein undergoes spontaneous rearrangement to a conformation having features in common with the infectious form / Leclerc, E.; Peretz, D.; Ball, H.; Sakurai, H.; Legname, G.; Serban, A.; Prusiner, S. B.; Burton, D. R.; Williamson, R. A.. - In: EMBO JOURNAL. - ISSN 0261-4189. - 20:7(2001), pp. 1547-1554. [10.1093/emboj/20.7.1547]

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

Legname, G.;
2001-01-01

Abstract

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.
2001
20
7
1547
1554
10.1093/emboj/20.7.1547
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC145482/
Leclerc, E.; Peretz, D.; Ball, H.; Sakurai, H.; Legname, G.; Serban, A.; Prusiner, S. B.; Burton, D. R.; Williamson, R. A.
File in questo prodotto:
File Dimensione Formato  
Leclerc_EMBOJ_2001.pdf

non disponibili

Licenza: Non specificato
Dimensione 174.97 kB
Formato Adobe PDF
174.97 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11767/17178
Citazioni
  • ???jsp.display-item.citation.pmc??? 13
  • Scopus 58
  • ???jsp.display-item.citation.isi??? 56
social impact