NR AYHT

AU Moudjou,M.; Bernard,J.; Sabuncu,E.; Langevin,C.; Laude,H.

TI Glycan chains modulate prion protein binding to immobilized metal ions

QU Neurochemistry International 2007 Apr; 50(5): 689-95

PT journal article; research support, non-u.s. gov't

AB PrPc is the normal isoform of the prion protein which can be converted into PrPsc, the pathology-associated conformer in prion diseases. It contains two N-linked glycan chains attached to the C-proximal globular domain. While the biological functions of PrPc are still unknown, its ability to bind Cu(2+) is well documented. The main Cu(2+)-binding sites are located in the N-proximal, unstructured region of the molecule. Here we report that PrPc glycans influence the capacity of PrPc from sheep brain or cultured Rov cells to bind IMAC columns loaded with Cu(2+) or Co(2+). Using different anti-PrP antibodies and PrPc glycosylation mutants, we show that the full length non-glycosylated form of PrPc has a higher binding efficiency for column-bound Cu(2+) and Co(2+) than the corresponding glycosylated form. Our findings raise the possibility that the accessibility of the PrPc metal ion-binding sites might be controlled by the glycan chains.

MH Animals; Brain/metabolism; Cell Line; Chromatography, Affinity/methods; Cobalt/*metabolism; Copper/*metabolism; Glycosylation; Polysaccharides/*metabolism; PrPc Proteins/*metabolism; Rabbits; Sheep

AD Unite de Virologie et Immunologie Moleculaires, INRA, 78350 Jouy-en-Josas, France.

SP englisch

PO England

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