Copper(II) interaction with unstructured prion domain outside the octarepeat region: speciation, stability, and binding details of copper(II) complexes with PrP106-126 peptides.
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.
Di Natale
Giuseppe
G
Dipartimento di Scienze Chimiche, Università di Catania, Italy.
Grasso
Giulia
G
Impellizzeri
Giuseppe
G
La Mendola
Diego
D
Micera
Giovanni
G
Mihala
Nikolett
N
Nagy
Zoltán
Z
Osz
Katalin
K
Pappalardo
Giuseppe
G
Rigó
Viktória
V
Rizzarelli
Enrico
E
Sanna
Daniele
D
Sóvágó
Imre
I
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D004355:Drug Stability; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D011199:Potentiometry; D011328:Prions / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013053:Spectrophotometry
D010446:Peptide Fragments; D011328:Prions; D003300:Copper