The comprehensive native interactome of a fully functional tagged prion protein.
PLoS One
; 4(2): e4446, 2009.
Article
en En
| MEDLINE
| ID: mdl-19209230
ABSTRACT
The enumeration of the interaction partners of the cellular prion protein, PrP(C), may help clarifying its elusive molecular function. Here we added a carboxy proximal myc epitope tag to PrP(C). When expressed in transgenic mice, PrP(myc) carried a GPI anchor, was targeted to lipid rafts, and was glycosylated similarly to PrP(C). PrP(myc) antagonized the toxicity of truncated PrP, restored prion infectibility of PrP(C)-deficient mice, and was physically incorporated into PrP(Sc) aggregates, indicating that it possessed all functional characteristics of genuine PrP(C). We then immunopurified myc epitope-containing protein complexes from PrP(myc) transgenic mouse brains. Gentle differential elution with epitope-mimetic decapeptides, or a scrambled version thereof, yielded 96 specifically released proteins. Quantitative mass spectrometry with isotope-coded tags identified seven proteins which co-eluted equimolarly with PrP(C) and may represent component of a multiprotein complex. Selected PrP(C) interactors were validated using independent methods. Several of these proteins appear to exert functions in axomyelinic maintenance.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Recombinantes de Fusión
/
Priones
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Suiza