NR APRI
AU Morante,S.; Gonzalez-Iglesias,R.; Potrich,C.; Meneghini,C.; Meyer-Klaucke,W.; Menestrina,G.; Gasset,M.
TI Inter- and intra-octarepeat Cu(II) site geometries in the prion protein: Implications in Cu(II) binding cooperativity and Cu(II)-mediated assemblies.
QU The Journal of Biological Chemistry 2003 Dec 31
PT journal article
AB Cu(II) binding to alphaPrP can be both intramolecular and intermolecular. X-ray absorption spectroscopy at the Cu K-edge has been used to explore the site geometry under each binding mode using both insoluble polymeric Cu(II)-alphaBoPrP(24-242) complexes and soluble Cu(II) complexes of peptides containing one, two and four copies of the octarepeat. Analysis of the extended region of the spectra using a multiple-scattering approach, revealed two types of sites differing in the number of His residues in the first coordination shell of Cu(II). Peptides containing 1 and 2 octarepeat copies in sub-stoichiometric Cu(II)-complexes, showed the direct binding of a single His in acord with crystallographic intra-repeat geometry. Alternatively, polymeric Cu(II)-alphaBoPrP(24-242) complex and Cu(II) in its soluble complex with a 4-octarepeat peptide at half site-occupancy, showed Cu(II) directly bound to two His consistent with an inter-repeat binding mode. Increasing the Cu(II) site occupancy from 0.5 to 0.75 in the peptide containing four octarepeats resulted in spectral features that are intermediate to those for the inter- and of the intra-repeat modes. The transition from His-Cu-His (inter-repeat) to Cu-His (intra-repeat) on increasing Cu(II) saturation offers a structural basis for the positive cooperativity of the cation binding process and explains the capacity of alphaPrP to participate in Cu(II)-mediated intermolecular interactions.
AD Insto Qumica-Fsica Rocasolano, Consejo Superior de Investigaciones Cientficas (CSIC), Madrid, Madrid E-28006.
SP englisch