Proline and glycine control protein self-organization into elastomeric or amyloid fibrils.

Elastin provides extensible tissues, including arteries and skin, with the propensity for elastic recoil, whereas amyloid fibrils are associated with tissue-degenerative diseases, such as Alzheimer's. Although both elastin-like and amyloid-like materials result from the self-organization of proteins into fibrils, the molecular basis of their differing physical properties is poorly understood. Using molecular simulations of monomeric and aggregated states, we demonstrate that elastin-like and amyloid-like peptides are separable on the basis of backbone hydration and peptide-peptide hydrogen bonding. The analysis of diverse sequences, including those of elastin, amyloids, spider silks, wheat gluten, and insect resilin, reveals a threshold in proline and glycine composition above which amyloid formation is impeded and elastomeric properties become apparent. The predictive capacity of this threshold is confirmed by the self-assembly of recombinant peptides into either amyloid or elastin-like fibrils. Our findings support a unified model of protein aggregation in which hydration and conformational disorder are fundamental requirements for elastomeric function.