Facial symmetry in protein self-assembly

Amyloids are self-assembled protein architectures implicated in dozens of misfolding diseases. These assemblies appear to emerge through a selection of specific conformational strains which nucleate and propagate within cells to cause disease. The short A beta(16-22) peptide, which includes the central core of the Alzheimer's disease A beta peptide, generates an amyloid fiber which is morphologically indistinguishable from the full-length peptide fiber, but it can also form other morphologies under distinct conditions. Here we combine spectroscopic and microscopy analyses that reveal the subtle atomic-level differences that dictate assembly of two conformationally pure A beta(16-22) assemblies, amyloid fibers and nanotubes, and define the minimal repeating unit for each assembly.