Skin gets its elasticity from elastin, which aggregates into fibrous assemblies. But at high local concentrations, almost any protein can aggregate into an amyloid, according to some proposals. So Pomès wondered, “If nature designs a protein that is supposed to aggregate, how does it avoid an amyloid state?” The key, he finds, is disorder-inducing amino acids.
Computer-simulated folding of peptides with elastin-like motifs in water revealed that constructing an elastomere requires a high degree of disorder and hydration. Such disorder only occurred when there was a threshold level of glycine and proline. Natural proteins that form amyloids fell at or below this calculated level, whereas the most elastic proteins, such as one type of spider silk, were far above the proline/glycine threshold.
Glycine, lacking any side chain, is so flexible that order is entropically unfavorable. Proline's cyclic side chain, by contrast, is “too stiff to make a regular secondary structure,” says Pomès. “Both [residues] contribute to disorder, but for opposite reasons.”