Cu2+ binding triggers alphaBoPrP assembly into insoluble laminar polymers.
Cu(2+) binding is so far the best characterized property of the prion protein. This interaction has been mapped to the N-terminal domain of the prion protein where multiple His residues occur largely embedded within the repetitive PHGGGWGQ sequence known as octarepeats. When Cu(2+) interaction is studied using a solution of full-length bovine prion protein containing six octarepeats at protein concentrations above 25 microM, a drastic increase in solution turbidity is observed due to the formation of insoluble cation-protein complexes that appear as bidimensional polymer meshes. These bidimensional meshes consist of a single layer of protein molecules crosslinked by Cu(2+) cations. Polymer formation is a cooperative process that proceeds by nucleation of protein molecules with a Cu(2+) site occupancy of above 2. These results support the hypothesis that the N-terminal domain of prion protein is a ligand binding module that promotes crosslinked assembly, and suggest the existence of inter-repeat Cu(2+) sites.
González-Iglesias
Reinerio
R
Instituto Química-Física 'Rocasolano', CSIC, Serrano 119, E-28006, Madrid, Spain.
Elvira
Gema
G
Rodríguez-Navarro
José A
JA
Vélez
Marisela
M
Calero
Miguel
M
Pajares
María A
MA
Gasset
María
M
D000595:Amino Acid Sequence; D000818:Animals; D002413:Cations, Divalent; D002417:Cattle; D003300:Copper / Q000737:chemistry / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D011108:Polymers / Q000737:chemistry*; D018621:PrPC Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D020449:Repetitive Sequences, Amino Acid; D012995:Solubility; D013053:Spectrophotometry / Q000379:methods
D002413:Cations, Divalent; D010446:Peptide Fragments; D011108:Polymers; D018621:PrPC Proteins; D003300:Copper