JMB-HEADER RAS-JOURNALS EIMB Pleiades Publishing

RUS

             

ENG

YearIMPACT-FACTOR
2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 49(2015) N 3 p. 450-456; DOI Interaction of intranuclear -amyloid with DNA is considered to be a plausible mechanism of Alzheime Full Text

S.A. Khmeleva1, Y.V. Mezentsev1,2, S.A. Kozin2, V.A. Mitkevich2, A.E. Medvedev1,2, A.S. Ivanov1, N.V. Bodoev1, A.A. Makarov2, S.P. Radko1,2*

Effect of mutations and modifications of amino acid residues on zinc-induced interaction of the metal-binding domain of β-amyloid with DNA

1Orekhovich Institute of Biomedical Chemistry, Moscow, 119121 Russia
2Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia

*radko@ibmc.msk.ru
Received - 2014-10-07; Accepted - 2014-10-20

Interaction of intranuclear β-amyloid with DNA is considered to be a plausible mechanism of Alzheimer's disease pathogenesis. The interaction of single- and double-stranded DNA with synthetic peptides was analyzed using surface plasmon resonance. The peptides represent the metal-binding domain of β-amyloid (amino acids 1-16) and its variants with chemical modifications and point substitutions of amino acid residues which are associated with enhanced neurotoxicity of β-amyloid in cell tests. It has been shown that the presence of zinc ions is necessary for the interaction of the peptides with DNA in solution. H6R substitution has remarkably reduced the ability of domain 1-16 to bind DNA. This is in accordance with the supposition that the coordination of a zinc ion by amino acid residues His6, Glu11, His13, and His14 of the β-amyloid metal-binding domain results in the occurrence of an anion-binding site responsible for the interaction of the domain with DNA. Zinc-induced dimerization and oligomerization of domain 1-16 associated with phosphorylation of Ser8 and the presence of unblocked amino- and carboxy-terminal groups have resulted in a decrease of peptide concentrations required for detection of the peptide-DNA interaction. The presence of multiple anion-binding sites on the dimers and oligomers is responsible for the enhancement of the peptide-DNA interaction. A substitution of the negatively charged residue Asp7 for the neutral residue Asn in close proximity to the anion-binding site of the domain 1-16 of Aβ facilitates the electrostatic interaction between this site and phosphates of a polynucleotide chain, which enhances zinc-induced binding to DNA.

Alzheimer's disease, β-amyloid, zinc, biosensor analysis



JMB-FOOTER RAS-JOURNALS