Glycan chains modulate prion protein binding to immobilized metal ions

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 Cu2+ is well documented. The main Cu2+-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 Cu2+ or Co2+. 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 Cu2+ and Co2+ 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.