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 Aβ(30-36) is juxtaposed with Aβ(17-23), Aβ(16-22), and Aβ(15-21). The Aβ(16-22)-Aβ(30-36) 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.