Glycan chains modulate prion protein binding to immobilized metal ions.
PrP(c) is the normal isoform of the prion protein which can be converted into PrP(Sc), 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 PrP(c) 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 PrP(c) glycans influence the capacity of PrP(c) from sheep brain or cultured Rov cells to bind IMAC columns loaded with Cu(2+) or Co(2+). Using different anti-PrP antibodies and PrP(c) glycosylation mutants, we show that the full length non-glycosylated form of PrP(c) 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 PrP(c) metal ion-binding sites might be controlled by the glycan chains.
Moudjou
Mohammed
M
Unité de Virologie et Immunologie Moléculaires, INRA, 78350 Jouy-en-Josas, France.
Bernard
Julie
J
Sabuncu
Elifsu
E
Langevin
Christelle
C
Laude
Hubert
H
D000818:Animals; D001921:Brain / Q000378:metabolism; D002460:Cell Line; D002846:Chromatography, Affinity / Q000379:methods; D003035:Cobalt / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D006031:Glycosylation; D011134:Polysaccharides / Q000378:metabolism*; D018621:PrPC Proteins / Q000378:metabolism*; D011817:Rabbits; D012756:Sheep
D011134:Polysaccharides; D018621:PrPC Proteins; D003035:Cobalt; D003300:Copper