期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 217, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2021.111358
关键词
R3 domain of tau protein; 2-histidine containing peptides; Copper(II) complexes; Potentiometry; Spectroscopy; Mass spectrometry
资金
- EU
- European Regional Development Fund [GINOP-2.3.2-15-2016-00008]
- Hungarian National Research, Development and Innovation Office [NKFIH K115480, 2019-2.1.11-TET-2019-00055]
- New National Excellence program of the Ministry of Human Capacities, Hungary [UNKP-19-2]
- MTA (Hungary) - CNR (Italy) bilateral program
The copper(II) complexes of a peptide fragment from the R3 domain of tau protein have been studied using various methods to determine their coordination modes. The versatile coordination of copper(II) with the peptide is attributed to the presence of two adjacent histidyl residues, resulting in different complex formations at varying metal-to-ligand ratios. CD spectroscopy indicates the presence of coordination isomers with similar concentrations.
The copper(II) complexes of a peptide fragment of the R3 domain of tau protein (tau(326-333) Ac-GNIHHKPG-NH2) and its mutants (Ac-GNGHHKPG-NH2, Ac-GNIHHKAG-NH2, Ac-GNGAHKPG-NH2 and Ac-GNGHAKPG-NH2) have been studied by potentiometric and spectroscopic (UV-Vis, CD) methods. ESR spectroscopy and mass spectrometry were also used to prove the coordination mode of the mononuclear complexes and the formation of dinuclear species, respectively. It has been demonstrated that the (326-333) fragment of tau protein is a versatile and effective ligand for copper(II) coordination. The versatility of copper(II) binding is related to the presence of two adjacent histidyl residues in the sequence, which results in the coexistence of mononuclear, bis(ligand) and dinuclear complexes at different metal to ligand ratios. The 1:1 mononuclear complexes are, however, the dominant species with all peptides and the imidazole-N and one to three deprotonated amide nitrogen atoms towards the N-terminal side of the histidyl residue have been suggested as metal binding sites. This binding mode allows the formation of coordination isomers because any of the two histidine moieties can be the primary anchoring site. It is evident from the CD spectroscopic measurements that the isomers are present in almost equal concentration. The copper(II) binding affinity of the native fragment of tau protein is comparable to that of a similar 2-histidine fragment of amyloid-beta mutant, Ac-SGAEGHHQK-NH2 but the comparison with an independent histidyl residue (H32) from the N-terminal region of the protein reveals the predominance of H32 over the histidines in the R3 domain.
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