Designed peptides that assemble into cross-alpha amyloid-like structures

Amyloids adopt `cross-beta' structures composed of long, twisted fibrils
with beta-strands running perpendicular to the fibril axis. Recently, a
toxic peptide was proposed to form amyloid-like cross-alpha structures
in solution, with a planar bilayer-like assembly observed in the crystal
structure. Here we crystallographically characterize designed peptides
that assemble into spiraling cross-alpha amyloid-like structures, which
resemble twisted beta-amyloid fibrils. The peptides form helical dimers,
stabilized by packing of small and apolar residues, and the dimers
further assemble into cross-alpha amyloid-like fibrils with superhelical
pitches ranging from 170 angstrom to 200 angstrom. When a small residue
that appeared critical for packing was converted to leucine, it resulted
in structural rearrangement to a helical polymer. Fluorescently tagged
versions of the designed peptides form puncta in mammalian cells, which
recover from photobleaching with markedly different kinetics. These
structural folds could be potentially useful for directing in vivo
protein assemblies with predetermined spacing and stabilities.