The cellular prion protein binds copper in vivo.

Abstract:

:The normal cellular form of prion protein (PrPC) is a precursor to the pathogenic protease-resistant forms (PrPSc) believed to cause scrapie, bovine spongiform encephalopathy (BSE) and Creutzfeldt-Jakob disease. Its amino terminus contains the octapeptide PHGGGWGQ, which is repeated four times and is among the best-preserved regions of mammalian PrPC. Here we show that the amino-terminal domain of PrPC exhibits five to six sites that bind copper (Cu(II)) presented as a glycine chelate. At neutral pH, binding occurs with positive cooperativity, with binding affinity compatible with estimates for extracellular, labile copper. Two lines of independently derived PrPC gene-ablated (Prnp0/0) mice exhibit severe reductions in the copper content of membrane-enriched brain extracts and similar reductions in synaptosomal and endosome-enriched subcellular fractions. Prnp0/0 mice also have altered cellular phenotypes, including a reduction in the activity of copper/zinc superoxide dismutase and altered electrophysiological responses in the presence of excess copper. These findings indicate that PrPC can exist in a Cu-metalloprotein form in vivo.

journal_name

Nature

journal_title

Nature

authors

Brown DR,Qin K,Herms JW,Madlung A,Manson J,Strome R,Fraser PE,Kruck T,von Bohlen A,Schulz-Schaeffer W,Giese A,Westaway D,Kretzschmar H

doi

10.1038/37783

subject

Has Abstract

pub_date

1997-12-18 00:00:00

pages

684-7

issue

6661

eissn

0028-0836

issn

1476-4687

journal_volume

390

pub_type

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