Glycan chains of Prion protein PrPc affect its metal ion-binding-activity - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2005

Glycan chains of Prion protein PrPc affect its metal ion-binding-activity

Résumé

PrPc is the normal isoform of the prion protein PrP, which can be converted into PrPsc, the pathology-associated conformer in TSE. PrPc contains two N-linked glycan chains located on the C-proximal globular domain. Although the PrPc functions are still unknown, its ability to bind Cu++ is well documented. The main Cu++-binding sites have been mapped to the N-proximal flexible tail of the molecule. Here we report that PrPc glycans modulate the capacity of PrPc prepared from sheep brain or cultured Rov cells to bind to Cu++- or Co++-loaded IMAC columns. Using different anti-PrP antibodies we showed that the full length nonglycosylated form of PrPc possess a higher affinity for transition metal ions than the glycosylated isoforms. Studies of the behaviour of PrPc glycosylation mutants expressed in Rov cells, and of Nterminally truncated (PrP103-234) or full length E.coli (PrP23-234) recombinant PrPs on IMAC columns provided evidence that the capacity of PrPc to bind metal ions at its N-proximal domain could be impaired by either one of the two glycan chains. This observation is consistent with the existence of an interaction between the flexible and globular domains of the prion protein. There is experimental evidence to indicate that the presence of glycan chains in PrP may affect the efficiency of conversion into PrPsc. Other studies have shown that PrPc incubated with transition metal cations acquires some properties of PrPsc (relative resistance to PK digestion, enrichment in beta-sheet content, aggregation and insolubility). Taken together, these and our present data raise the question of whether the higher affinity of unglycosylated PrP species for metal transition ions might contribute to explain their apparent increased ability to convert compared to glycosylated species.
Fichier non déposé

Dates et versions

hal-02759639 , version 1 (04-06-2020)

Identifiants

  • HAL Id : hal-02759639 , version 1
  • PRODINRA : 145337

Citer

Mohammed M. Moudjou, Julie Bernard, Christelle C. Langevin, Frédéric Eghiaian, Human Rezaei, et al.. Glycan chains of Prion protein PrPc affect its metal ion-binding-activity. Prion 2005, Oct 2005, Dusseldorf, Germany. ⟨hal-02759639⟩
4 Consultations
0 Téléchargements

Partager

Gmail Facebook X LinkedIn More