Polymorphism of oligomers of a peptide from ?-amyloid.

ABSTRACT: This contribution reports solution-phase structural studies of oligomers of a family of peptides derived from the ?-amyloid peptide (A?). We had previously reported the X-ray crystallographic structures of the oligomers and oligomer assemblies formed in the solid state by a macrocyclic ?-sheet peptide containing the A?(15-23) nonapeptide. In the current study, we set out to determine its assembly in aqueous solution. In the solid state, macrocyclic ?-sheet peptide 1 assembles to form hydrogen-bonded dimers that further assemble in a sandwich-like fashion to form tetramers through hydrophobic interactions between the faces bearing V18 and F20. In aqueous solution, macrocyclic ?-sheet peptide 1 and homologue 2a form hydrogen-bonded dimers that assemble to form tetramers through hydrophobic interactions between the faces bearing L17, F19, and A21. In the solid state, the hydrogen-bonded dimers are antiparallel, and the ?-strands are fully aligned, with residues 17-23 of one of the macrocycles aligned with residues 23-17 of the other. In solution, residues 17-23 of the hydrogen-bonded dimers are shifted out of alignment by two residues toward the C-termini. The two hydrogen-bonded dimers are nearly orthogonal in the solid state, while in solution the dimers are only slightly rotated. The differing morphology of the solution-state and solid-state tetramers is significant, because it may provide a glimpse into some of the structural bases for polymorphism among A? oligomers in Alzheimer's disease.

SUBMITTER: Pham JD 

PROVIDER: S-EPMC4004211 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature