title: Copper binding extrinsic to the octarepeat region in the prion protein.
abstract: Current research suggests that the function of the prion protein (PrP) is linked to its ability to bind copper. PrP is implicated in copper regulation, copper buffering and copper-dependent signaling. Moreover, in the development of prion disease, copper may modulate the rate of protein misfolding. PrP possesses a number of copper sites, each with distinct chemical characteristics. Most studies thus far have concentrated on elucidating chemical features of the octarepeat region (residues 60-91, hamster sequence), which can take up to four equivalents of copper, depending on the ratio of Cu2+ to protein. However, other sites have been proposed, including those at histidines 96 and 111, which are adjacent to the octarepeats, and also at histidines within PrP's folded C-terminal domain. Here, we review the literature of these copper sites extrinsic to the octarepeat region and add new findings and insights from recent experiments.
authors.affiliation: Department of Chemistry & Biochemistry, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. ewalter@chemistry.ucsc.edu
authors.forename: Eric D
authors.initials: ED
authors.lastname: Walter
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stevens
authors.forename: Ann R
authors.initials: AR
authors.lastname: Spevacek
authors.forename: Micah P
authors.initials: MP
authors.lastname: Visconte
authors.forename: Andrew
authors.initials: A
authors.lastname: Dei Rossi
authors.forename: Glenn L
authors.initials: GL
authors.lastname: Millhauser
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001671:Biochemistry / Q000379:methods*; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D011328:Prions / Q000737:chemistry*; D011485:Protein Binding; D011489:Protein Denaturation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D011328:Prions; D006639:Histidine; D003300:Copper