The prion protein (PrP(C)) shows cooperative copper binding of the N-terminal octarepeat (PHGGGWGO) x4. In brain homogenates, PrP(C) is found in highest concentration in synaptosomal fractions. Mice devoid of PrP(C) (Prnp0/0 mice) show synaptosomal copper concentrations diminished by 50% as compared to normal mice. PrP(C) in the synaptic cleft may serve as a copper buffer. Alternatively it may play a role in the re-uptake of copper into the presynapse or may be of structural importance for the N-terminus and thus may influence binding of PrP(C) to other proteins.