Thermodynamics and structural characterization of the nickel(<scp>ii</scp>) and zinc(<scp>ii</scp>) complexes of various peptide fragments of tau protein

Balogh, Bettina Diána; Szunyog, Györgyi; Lukács, Márton; Szakács, Bence; Sóvágó, Imre; Várnagy, Katalin

doi:10.1039/d1dt02324a

Cited by 9 publications

(17 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our simulation and experimental studies confirm the ability of NH6 peptides to modulate the conformation of the PGGG motif. The presence of conserved histidine residues in NH6 peptides, whose conformations are sensitive to tautomerism, − pH, , and metal-ion affinity, − could also play a major role in modulating aggregation.…”

Section: Discussionmentioning

confidence: 99%

Sequence-Dependent Conformational Properties of PGGG Motif in Tau Repeats: Insights from Molecular Dynamics Simulations of Narrow Pick Filament

Sahayaraj

Viswanathan

Pinhero

et al. 2022

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Tauopathies are a class of neurodegenerative diseases correlated with the presence of pathological Tau fibrils as a diagnostic marker. The microtubule-binding repeat region of Tau protein, which includes R1, R2, R3, and R4 repeats, constitutes the core of these fibrils. Each repeat consists of a semiconserved C-terminal hexapeptide flanked by KxGS and PGGG motifs. Previous studies have shown the influence of these peptides on protein aggregation, yet their repeat-specific properties are less explored. Using molecular dynamics, we probed the sequence-specific influence of the C-terminal hexapeptide (264ENLKHQ269) in determining the compact local conformation of the R1 repeat of the narrow Pick filament (NPF) with a homologous E264G mutation. In addition to that, we also studied the influence of 262S phosphorylation on this conformation as the phosphorylation is proposed to alleviate the pathogenesis of Pick’s disease. Interestingly, we determined that E264G mutation induces a conformational shift of 270PGGG273 from a turn to a random coil. This conformational dependence is experimentally verified with the R1R3-E264G mutant construct, which displayed accelerated aggregation compared with the R1R3 wild-type construct. A significant delay in aggregation of the R1R3-G326E mutant further demonstrates the importance of 326G in determining the conformation of the R3 repeat. Thus, we conclude that the conformational properties of the PGGG motif in Tau repeats are strongly dependent on the repeat-specific sequence of the C-terminal hexapeptide.

show abstract

Section: Discussionmentioning

confidence: 99%

Sequence-Dependent Conformational Properties of PGGG Motif in Tau Repeats: Insights from Molecular Dynamics Simulations of Narrow Pick Filament

Sahayaraj

Viswanathan

Pinhero

et al. 2022

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…On the contrary, His14 and His32 has only low zinc(II) binding affinity and the Zn(II)-Nim coordinated species cannot compete with the hydrolytic reactions of the metal ions. The amide coordinated zinc(II) complexes of tau(326-333), however, predominate in the slightly alkaline samples [23]. Now in this paper we report the results of combined potentiometric and spectroscopic studies for the copper (II), zinc(II) and nickel(II) complexes of three other peptide fragments of tau protein: tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2).…”

Section: Introductionmentioning

confidence: 92%

Copper(II), Nickel(II) and Zinc(II) Complexes of Peptide Fragments of Tau Protein

Kastal,

Balabán,

Vida

et al. 2024

Preprint

View full text Add to dashboard Cite

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions but in case of copper(II) and nickel(II) the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ion but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relative low thermodynamic stability with these peptides. Copper(II) catalyzed oxidation of the peptides was also studied. In the presence of H2O2 the fragmentation of peptides can be detected in all cases. In the simultaneous presence of of H2O2 and ascorbic acid the extent of the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.

show abstract

“…Короткие пептиды представляют интерес как сами по себе, так и в качестве моделей для исследования фрагментов белковых молекул. Аналитические и клинические данные подтверждают, что ионы переходных металлов играют значительную роль в конформационных изменениях и последующей агрегации белков [33].…”

Section: таблицаunclassified

Theoretical and Experimental Approaches in the Study of Electrochemical and Thermodynamic Properties of Polyfunctional Organic Compounds in Liquid-Phase and Heterophase Systems

2023

Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.

View full text Add to dashboard Cite

The publication reflects the experimental substantiation and fundamental development of some important ideas of the theory of the mutual influence of functional substitution in complex molecules of macrocyclic and chelating compounds on their coordination, solvation and redox properties, as well as the formation of algorithms for searching useful functions of these compounds. Researchers of the Analytical Chemistry Department of the Ivanovo State University of Chemistry and Technology have been studying the electrochemical and thermodynamic behavior of porphyrins, complexones, amino acids, peptides and the corresponding complexes with d- and f-metal ions, their influence on coordination, solvation and catalytic processes for a number of years. The results obtained together with the literature data are discussed in the review. For citation: Bazanov M.I., Berezina N.M., Gridchin S.N., Krutova O.N., Gorboletova G.G., Bychkova S.A., Lytkin A.I., Chernyavskaya N.V., Chernikov V.V., Volkov A.V. Theoretical and experimental approaches in the study of electrochemical and thermodynamic properties of polyfunctional organic compounds in liquid-phase and heterophase systems. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2023. V. 66. N 7. P. 98-110. DOI: 10.6060/ivkkt.20236607. 6839j.

show abstract

Thermodynamics and structural characterization of the nickel(ii) and zinc(ii) complexes of various peptide fragments of tau protein

Abstract: Nickel(II) and zinc(II) complexes of various peptide fragments of tau protein have been investigated by potentiometric, UV-Vis, CD and ESI-MS techniques. The peptides include the native fragment tau(9-16) (Ac-EVMEDHAG-NH2), the...

Cited by 9 publications

References 33 publications

Sequence-Dependent Conformational Properties of PGGG Motif in Tau Repeats: Insights from Molecular Dynamics Simulations of Narrow Pick Filament

Sequence-Dependent Conformational Properties of PGGG Motif in Tau Repeats: Insights from Molecular Dynamics Simulations of Narrow Pick Filament

Copper(II), Nickel(II) and Zinc(II) Complexes of Peptide Fragments of Tau Protein

Theoretical and Experimental Approaches in the Study of Electrochemical and Thermodynamic Properties of Polyfunctional Organic Compounds in Liquid-Phase and Heterophase Systems

Contact Info

Product

Resources

About