NMR studies of the Zn2+ interactions with rat and human beta-amyloid (1-28) peptides in water-micelle environment.
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.
Gaggelli
Elena
E
Department of Chemistry, University of Siena, via Aldo Moro, 53-100 Siena, Italy.
Janicka-Klos
Anna
A
Jankowska
Elzbieta
E
Kozlowski
Henryk
H
Migliorini
Caterina
C
Molteni
Elena
E
Valensin
Daniela
D
Valensin
Gianni
G
Wieczerzak
Ewa
E
D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D002413:Cations, Divalent / Q000737:chemistry; D003198:Computer Simulation; D006801:Humans; D008823:Micelles; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D011522:Protons; D051381:Rats; D014867:Water / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D002413:Cations, Divalent; D008823:Micelles; D010446:Peptide Fragments; D011522:Protons; C084358:amyloid beta-protein (1-28); D014867:Water; D015032:Zinc