Title
Copper(II) Coordination Abilities of the Tau Protein’s N‐Terminus Peptide Fragments: A Combined Potentiometric, Spectroscopic and Mass Spectrometric Study
Author
Márton Lukács, Györgyi Szunyog, Ágnes Grenács, Norbert Lihi, Csilla Kállay, Giuseppe Di Natale, Tiziana Campagna, Valeria Lanza, Giovanni Tabbi, Giuseppe Pappalardo, Imre Sóvágó, Katalin Várnagy
Year
2019
Journal
ChemPlusChem
Abstract
Copper(II) complexes of the N‐terminal peptide fragments of tau protein have been studied by potentiometric and various spectroscopic techniques (UV‐vis, CD, ESR and ESI‐MS). The octapeptide Tau(9‐16) (Ac−EVMEDHAG−NH2) contains the H14 residue of the native protein, while Tau(26‐33) (Ac−QGGYTMHQ−NH2) and its mutants Tau(Q26K‐Q33K) (Ac−KGGYTMHK−NH2) and Tau(Q26K‐Y29A‐Q33K) (Ac−KGGATMHK−NH2) include the H32 residue. To compare the binding ability of H14 and H32 in a single molecule the decapeptide Ac−EDHAGTMHQD−NH2 (Tau(12‐16)(30‐34)) has also been synthesized and studied. The histidyl residue is the primary metal binding site for metal ions in all the peptide models studied. In the case of Tau(9‐16) the side chain carboxylate functions enhance the stability of the M−Nim coordinated complexes compared to Tau(26‐33) (logK(Cu−Nim)=5.04 and 3.78, respectively). Deprotonation and metal ion coordination of amide groups occur around the physiological pH range for copper(II). The formation of the imidazole‐ and amide‐coordinated species changes the metal ion preference and the complexes formed with the peptides containing the H32 residue predominate over those of H14 at physiological pH values (90 %–10 %) and in alkaline samples (96 %–4 %).
Instrument
J-810
Keywords
Circular dichroism, Protein structure, Secondary structure, Coordination chemistry, Chemial stability, Ligand binding, Inorganic chemistry, Biochemistry