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.
Rauscher
Sarah
S
Molecular Structure and Function Programme, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.
Baud
Stéphanie
S
Miao
Ming
M
Keeley
Fred W
FW
Pomès
Régis
R
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry; D000818:Animals; D052160:Benzothiazoles; D002645:Chickens; D004549:Elastin / Q000737:chemistry; D019277:Entropy; D005998:Glycine / Q000737:chemistry*; D006801:Humans; D007313:Insecta; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D011487:Protein Conformation; D013844:Thiazoles / Q000737:chemistry; D014908:Triticum
D000682:Amyloid; D052160:Benzothiazoles; D010455:Peptides; D013844:Thiazoles; C009462:thioflavin T; D004549:Elastin; D011392:Proline; D005998:Glycine