| Autor: |
Cristina Potrich, María Gasset, Carlo Meneghini, Silvia Morante, Wolfram Meyer-Klaucke, Gianfranco Menestrina, Reinerio González-Iglesias |
| Rok vydání: |
2004 |
| Předmět: |
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| Zdroj: |
Journal of Biological Chemistry. 279:11753-11759 |
| ISSN: |
0021-9258 |
| Popis: |
Cu(II) binding to the α prion protein (αPrP) can be both intramolecular and intermolecular. X-ray absorption spectroscopy at the copper K-edge has been used to explore the site geometry under each binding mode using both insoluble polymeric Cu(II)·αBoPrP-(24-242) (bovine PrP) 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 one and two-octarepeat copies in sub-stoichiometric Cu(II) complexes showed the direct binding of a single His in accord with crystallographic intra-repeat geometry. Alternatively, the polymeric Cu(II)·αBoPrP-(24-242) complex and Cu(II) in its soluble complex with a four-octarepeat peptide at half-site-occupancy showed Cu(II) directly bound to two His residues, 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 of the inter- and 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 αPrP to participate in Cu(II)-mediated intermolecular interactions. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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