A Binuclear Zinc Interaction Fold Discovered in the Homodimer of Alzheimer's Amyloid-β Fragment with Taiwanese Mutation D7H

Angew Chem Int Ed Engl. 2017 Sep 18;56(39):11734-11739. doi: 10.1002/anie.201704615. Epub 2017 Jun 27.


Zinc-induced oligomerization of amyloid-β peptide (Aβ) produces potentially pathogenic agents of Alzheimer's disease. Mutations and modifications in the metal binding domain 1-16 of Aβ peptide crucially affect its zinc-induced oligomerization by changing intermolecular zinc mediated interface. The 3D structure of this interface appearing in a range of Aβ species is a prospective drug target for disease modifying therapy. Using NMR spectroscopy, EXAFS spectroscopy, mass spectrometry, and isothermal titration calorimetry the interaction of zinc ions with Aβ fragments 1-7 and 1-10 carrying familial Taiwanese mutation D7H was studied. Zinc ions induce formation of a stable homodimer formed by the two peptide chains fastened by two zinc ions and stacking interactions of imidazole rings. A binuclear zinc interaction fold in the dimer structure was discovered. It can be used for designing zinc-regulated proteins and zinc-mediated self-assembling peptides.

Keywords: Alzheimer's amyloid β-peptide; NMR spectroscopy; solution structure; zinc binding; zinc-peptide complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Protein Precursor / chemistry
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism*
  • Binding Sites
  • Calorimetry / methods
  • Dimerization
  • Humans
  • Mutation*
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Binding
  • Protein Conformation
  • X-Ray Absorption Spectroscopy
  • Zinc / chemistry
  • Zinc / metabolism*


  • APP protein, human
  • Amyloid beta-Protein Precursor
  • Peptide Fragments
  • Zinc