The N-terminal tandem repeat region of human prion protein reduces copper: role of tryptophan residues.
Prion protein (PrP) has attracted considerable attention, mainly due to its involvement in transmissible spongiform encephalopathies. Toward its N-terminal region, PrP bears an octapeptide repeat which has been shown to bind copper. We found that a human synthetic peptide (PrP(59-91)), corresponding to the four repeats of Pro-His-Gly-Gly-Gly-Trp-Gly-Gln has the ability to reduce copper. A mutant peptide lacking tryptophan displayed only 24% of the wild-type copper-reducing activity. Experiments performed in a N(2) environment confirmed that O(2) is not involved in the reaction. Our results indicated that cell surface PrP, besides its ability to bind copper, bears the capacity to reduce copper in vitro. The potential physiological role of copper reduction by PrP is discussed.
Ruiz
F H
FH
Centro de Regulación Celular y Patología, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, 114-D, Chile.
Silva
E
E
Inestrosa
N C
NC
D003300:Copper / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020080:Tandem Repeat Sequences; D014364:Tryptophan / Q000378:metabolism*
D011328:Prions; D003300:Copper; D014364:Tryptophan; D010100:Oxygen