NR APUR
AU Gonzalez-Iglesias,R.; Elvira,G.; Rodriguez-Navarro,J.A.; Velez,M.; Calero,M.; Pajares,M.A.; Gasset,M.
TI Cu2+ binding triggers alphaBoPrP assembly into insoluble laminar polymers
QU FEBS Letters 2004 Jan 2; 556(1-3): 161-6
PT journal article
AB 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.
MH Amino Acid Sequence; Animals; Cations, Divalent; Cattle; Copper/chemistry/*metabolism; Microscopy, Atomic Force; Molecular Sequence Data; Peptide Fragments/chemistry/metabolism; Polymers/*chemistry; PrPc Proteins/*chemistry/metabolism; Protein Binding; Repetitive Sequences, Amino Acid; Solubility; Spectrophotometry/methods; Support, Non-U.S. Gov't
AD Instituto Quimica-Fisica 'Rocasolano', CSIC, Serrano 119, E-28006, Madrid, Spain.
SP englisch
PO Niederlande