X-ray Crystallographic Structure of a Compact Dodecamer from a Peptide Derived from Aβ16-36

Org Lett. 2017 Jul 7;19(13):3462-3465. doi: 10.1021/acs.orglett.7b01445. Epub 2017 Jun 15.

Abstract

The assembly of the β-amyloid peptide, Aβ, into soluble oligomers is associated with neurodegeneration in Alzheimer's disease. The Aβ oligomers are thought to be composed of β-hairpins. Here, the effect of shifting the residue pairing of the β-hairpins on the structures of the oligomers that form is explored through X-ray crystallography. Three residue pairings were investigated using constrained macrocyclic β-hairpins in which Aβ30-36 is juxtaposed with Aβ17-23, Aβ16-22, and Aβ15-21. The Aβ16-22-Aβ30-36 pairing forms a compact ball-shaped dodecamer composed of fused triangular trimers. This dodecamer may help explain the structures of the trimers and dodecamers formed by full-length Aβ.

Publication types

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

MeSH terms

  • Amyloid beta-Peptides / chemistry*
  • Crystallography, X-Ray
  • Models, Molecular
  • Molecular Structure
  • Peptide Fragments
  • X-Rays

Substances

  • Amyloid beta-Peptides
  • Peptide Fragments