Evaluation of copper2+ affinities for the prion protein.
The prion protein (PrP) is a cell-surface Cu2+ binding glycoprotein which can bind six copper ions. The role of Cu2+ in PrP function, misfolding, and prion disease has generated much interest; however, the field has been hampered by a lack of consensus with regard to the affinity of Cu2+ for PrPC. Here we build on our understanding of the appearance of visible CD spectra for full-length PrP and fragments to determine the affinity of Cu2+ for four different binding modes, with dissociation constants ranging between 13 and 66 nM at pH 7.4.
Nadal
Rebecca C
RC
School of Biological and Chemical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, UK.
Davies
Paul
P
Brown
David R
DR
Viles
John H
JH
D000818:Animals; D002942:Circular Dichroism; D003300:Copper / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005998:Glycine / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism; D011328:Prions / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D014364:Tryptophan / Q000737:chemistry
D010446:Peptide Fragments; D018621:PrPC Proteins; D011328:Prions; D003300:Copper; D014364:Tryptophan; D005998:Glycine