Modulating amyloid self-assembly and fibril morphology with Zn(II)

J Am Chem Soc. 2006 Mar 22;128(11):3540-2. doi: 10.1021/ja055973j.

Abstract

Metal ions (Zn(II)) are demonstrated as probes of amyloid structure in simple segments of the Abeta peptide, Abeta(13-21). By restricting the possible metal binding sites to His13/His14 dyad, we show that Zn2+ can specifically control the rate of self-assembly and dramatically regulate amyloid morphology via distinct coordination environments as characterized by X-ray absorption spectroscopy. The data establish that the single His13 is sufficient to coordinate Zn2+ productively for typical amyloid fiber formation, while a distinct Zn2+ coordination environment can be accessed in the presence of His13/Hi14 dyad to stabilize sheet/sheet associations and the transition to a ribbon/tube morphology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyloid / chemical synthesis
  • Amyloid / chemistry*
  • Amyloid / metabolism
  • Amyloid beta-Peptides / chemistry
  • Amyloid beta-Peptides / metabolism
  • Binding Sites
  • Cations, Divalent
  • Circular Dichroism
  • Models, Molecular
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Protein Structure, Secondary
  • Zinc / chemistry*

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Cations, Divalent
  • Peptide Fragments
  • Zinc