Localization of zinc binding sites of Ab1-16 with English mutation during formation of monomers and dimers with zinc

Maria Indeykina, Alexey Kononikhin, Igor Popov, Yury Kostyukevich, Alexandra Kulikova, Vladimir Mitkevich, Sergey Kozin, Alexander Makarov, Eugene Nikolaev

    Research output: Contribution to journalArticlepeer-review

    2 Citations (Scopus)


    Alzheimer's disease is characterized by oligomerization and aggregation of amyloid-beta. One of the key agents in these pathological processes are zinc ions. Beta-amyloid interacts with zinc ions through its metal-binding domain 1–16. Synthetic peptides corresponding to Aβ1–16 are good soluble models to study zinc binding to Aβ. There are several known mutations in this domain associated with familial early-onset AD: English H6R, Tottori D7N, Taiwan D7H. The English mutation is of special interest since it affects one of the four amino-acid residues known to form the coordination sphere for the zinc ion in the native Aβ peptide. It has been shown that the English mutation increases neurotoxicity of respective H6R-Aβ oligomers and accelerates H6R-Aβ fibril formation, this may be due with the impact of the mutation on zinc ion chelation, since H6 stabilizes the monomer of the native amyloid-beta, preventing it from further dimerization. In the presented work structure of zinc bound complexes of H6R-Aβ1-16 were investigated using mass-spectrometric approaches. It has been shown that the monomer of H6R-Aβ1-16 binds zinc in quite a different manner than the native Aβ peptide.

    Original languageEnglish
    Pages (from-to)67-72
    Number of pages6
    JournalInternational Journal of Mass Spectrometry
    Publication statusPublished - 1 Nov 2016


    • Amyloid
    • ESI
    • FT ICR
    • Mass spectrometry
    • Metal ions
    • Metal-peptide complexes


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