title: Cu2+ binding triggers alphaBoPrP assembly into insoluble laminar polymers.
abstract: 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.
authors.affiliation: Instituto Química-Física 'Rocasolano', CSIC, Serrano 119, E-28006, Madrid, Spain.
authors.forename: Reinerio
authors.initials: R
authors.lastname: González-Iglesias
authors.forename: Gema
authors.initials: G
authors.lastname: Elvira
authors.forename: José A
authors.initials: JA
authors.lastname: Rodríguez-Navarro
authors.forename: Marisela
authors.initials: M
authors.lastname: Vélez
authors.forename: Miguel
authors.initials: M
authors.lastname: Calero
authors.forename: María A
authors.initials: MA
authors.lastname: Pajares
authors.forename: María
authors.initials: M
authors.lastname: Gasset
mesh_terms: 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
chemical_list: D002413:Cations, Divalent; D010446:Peptide Fragments; D011108:Polymers; D018621:PrPC Proteins; D003300:Copper