NMR studies of the Zn2+ interactions with rat and human beta-amyloid (1-28) peptides in water-micelle environment

J Phys Chem B. 2008 Jan 10;112(1):100-9. doi: 10.1021/jp075168m. Epub 2007 Dec 12.

Abstract

Alzheimer's disease is a fatal neurodegenerative disorder involving the abnormal accumulation and deposition of peptides (amyloid-beta, Abeta) derived from the amyloid precursor protein. Here, we present the structure and the Zn2+ binding sites of human and rat Abeta(1-28) fragments in water/sodium dodecyl sulfate (SDS) micelles by using 1H NMR spectroscopy. The chemical shift variations measured after Zn2+ addition at T>310 K allowed us to assign the binding donor atoms in both rat and human zinc complexes. The Asp-1 amine, His-6 Ndelta, Glu-11 COO-, and His-13 Nepsilon of rat Abeta28 all enter the metal coordination sphere, while His-6 Ndelta, His-13, His-14 Nepsilon, Asp-1 amine, and/or Glu-11 COO- are all bound to Zn2+ in the case of human Abeta28. Finally, a comparison between the rat and human binding abilities was discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid beta-Peptides / chemistry*
  • Animals
  • Cations, Divalent / chemistry
  • Computer Simulation
  • Humans
  • Micelles*
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Peptide Fragments / chemistry*
  • Protein Structure, Tertiary
  • Protons
  • Rats
  • Water / chemistry*
  • Zinc / chemistry*

Substances

  • Amyloid beta-Peptides
  • Cations, Divalent
  • Micelles
  • Peptide Fragments
  • Protons
  • amyloid beta-protein (1-28)
  • Water
  • Zinc