Pubblicazioni

Autori:

Tagliavini, Fabrizio; Lievens, Patricia; Tranchant, Christine; Warter, Jean Marie; Mohr, Michel; Giaccone, Giorgio; Perini, Francesco; Rossi, Giacomina; Salmona, Mario; Piccardo, Pedro; Ghetti, Bernardino; Beavis, Ronald C.; Bugiani, Orso; Frangione, Blas; Prelli, Frances

Titolo:

A 7-kDa prion protein (PrP) fragment, an integral component of the PrP region required for infectivity, is the major amyloid protein in Gerstmann-Sträussler-Scheinker disease A117V.

Anno:

2001

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Referee:

Sì

Nome rivista:

JBC

ISSN Rivista:

0021-9258

N° Volume:

276

Intervallo pagine:

6009-6015

Parole chiave:

prion protein; Gerstmann-Sträussler-Scheinker (GSS) disease; Amyoid

Breve descrizione dei contenuti:

Gerstmann-Stra ̈ ussler-Scheinker disease (GSS) is a cerebral amyloidosis associated with mutations in the prion protein (PrP) gene (PRNP). The aim of this study was to characterize amyloid peptides purified from brain tissue of a patient with the A117V mutation who was Met/Val heterozygous at codon 129, Val129 being in coupling phase with mutant Val117. The major peptide extracted from amyloid fibrils was a 7-kDa PrP frag- ment. Sequence analysis and mass spectrometry showed that this fragment had ragged N and C termini, starting mainly at Gly88 and Gly90 and ending with Arg148, Glu152, or Asn153. Only Val was present at positions 117 and 129, indicating that the amyloid protein originated from mu- tant PrP molecules. In addition to the 7-kDa peptides, the amyloid fraction contained N- and C-terminal PrP fragments corresponding to residues 23– 41, 191–205, and 217–228. Fibrillogenesis in vitro with synthetic pep- tides corresponding to PrP fragments extracted from brain tissue showed that peptide PrP-(85–148) readily assembled into amyloid fibrils. Peptide PrP-(191–205) also formed fibrillary structures although with different morphology, whereas peptides PrP-(23– 41) and PrP-(217–228) did not. These findings suggest that the processing of mutant PrP isoforms associated with Gerstmann-Stra ̈ussler-Scheinker disease may occur ex- tracellularly. It is conceivable that full-length PrP and/or large PrP peptides are deposited in the extracel- lular compartment, partially degraded by proteases and further digested by tissue endopeptidases, originating a 7-kDa protease-resistant core that is similar in pa- tients with different mutations. Furthermore, the pres- ent data suggest that C-terminal fragments of PrP may participate in amyloid formation.

Id prodotto:

81022

Handle IRIS:

11562/581551

depositato il:

30 aprile 2014

ultima modifica:

10 novembre 2022

Citazione bibliografica:

Tagliavini, Fabrizio; Lievens, Patricia; Tranchant, Christine; Warter, Jean Marie; Mohr, Michel; Giaccone, Giorgio; Perini, Francesco; Rossi, Giacomina; Salmona, Mario; Piccardo, Pedro; Ghetti, Bernardino; Beavis, Ronald C.; Bugiani, Orso; Frangione, Blas; Prelli, Frances, A 7-kDa prion protein (PrP) fragment, an integral component of the PrP region required for infectivity, is the major amyloid protein in Gerstmann-Sträussler-Scheinker disease A117V. «JBC» , vol. 276 , 2001 , pp. 6009-6015

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