[Effects of the H6R and D7H Mutations on the Heparin-Dependent Modulation of Zinc-Induced Aggregation of Amyloid β].

Autor:	Radko SP; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.; Orekhovich Institute of Biomedical Chemistry, Moscow, 119121 Russia.; radkos@yandex.ru., Khmeleva SA; Orekhovich Institute of Biomedical Chemistry, Moscow, 119121 Russia., Kiseleva YY; Russian Scientific Center of Roentgenoradiology, Moscow, 117485 Russia., Kozin SA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia., Mitkevich VA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia., Makarov AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Jazyk:	ruština
Zdroj:	Molekuliarnaia biologiia [Mol Biol (Mosk)] 2019 Nov-Dec; Vol. 53 (6), pp. 1049-1056.
DOI:	10.1134/S0026898419060144
Abstrakt:	Zinc ions and glycosaminoglycans (GAGs) are found in amyloid deposits and are known to modulate the β-amyloid peptide (Aβ) aggregation, which is thought to be a key event in the pathogenesis of Alzheimer's disease (AD). Correlation spectroscopy was used to study how the H6R and D7H mutations of the metal-binding domain (MBD) of Aβ42 affect the modulation of its zinc-induced aggregation by the model GAG heparin. The H6R mutation was shown to decrease and the D7H mutation to increase the Aβ42 propensity to aggregate in the presence of zinc ions. In addition, H6R diminished and D7H enhanced the modulating effect of heparin. The difference in the heparin-dependent modulation was associated with coordination of zinc ions within the MBDs of the mutant peptides. The findings indicate that anion-binding sites formed by complexes of zinc ions with the Aβ MBD play an essential role in the interaction of zinc-induced Aβ aggregates with heparin.
Databáze:	MEDLINE
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