Copper(II) interaction with unstructured prion domain outside the octarepeat region: Speciation, stability, and binding details of copper(II) complexes with PrP106-126 peptides

Giuseppe Di Natale, Giulia Grasso, Giuseppe Impellizzeri, Diego La Mendola, Giovanni Micera, Nikolett Mihala, Zoltán Nagy, Katalin Õsz, Giuseppe Pappalardo, Viktória Rigó, Enrico Rizzarelli, Daniele Sanna, Imre Sóvágó

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Abstract

Copper(II) complexes of the neurotoxic peptide fragments of human and chicken prion proteins were studied by potentiometric, UV-vis, CD, and EPR spectroscopic and ESI-MS methods. The peptides included the terminally blocked native and scrambled sequences of HuPrP106-126 (HuPrPAc106-126NH2 and ScrHuPrPAc106-126NH2) and also the nona- and tetrapeptide fragments of both the human and chicken prion proteins (HuPrPAc106-114NH2, ChPrPAc119-127NH2, HuPrPAc109-112NH2, and ChPrPAc122-125NH2). The histidyl imidazole-N donor atoms were found to be the major copper(II) binding sites of all peptides; 3N and 4N complexes containing additional 2 and 3 deprotonated amide-N donors, respectively, are the major species in the physiological pH range. The complex formation processes for nona- and tetrapeptides are very similar, supporting the fact that successive deprotonation and metal ion coordination of amide functions go toward the N-termini in the form of joined six- and five-membered chelates. As a consequence, the peptide sequences investigated here, related to the neurotoxic region of the human PrP106-126 sequence, show a higher metal-binding affinity than the octarepeat fragments. In the case of the HuPrP peptide sequences, a weak pH-dependent binding of the Met109 residue was also detected in the 3N-coordinated complexes.

Original languageEnglish
Pages (from-to)7214-7225
Number of pages12
JournalInorganic Chemistry
Volume44
Issue number20
DOIs
Publication statusPublished - Oct 3 2005

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ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

Cite this

Di Natale, G., Grasso, G., Impellizzeri, G., La Mendola, D., Micera, G., Mihala, N., Nagy, Z., Õsz, K., Pappalardo, G., Rigó, V., Rizzarelli, E., Sanna, D., & Sóvágó, I. (2005). Copper(II) interaction with unstructured prion domain outside the octarepeat region: Speciation, stability, and binding details of copper(II) complexes with PrP106-126 peptides. Inorganic Chemistry, 44(20), 7214-7225. https://doi.org/10.1021/ic050754k