Short peptides self-assemble to produce catalytic amyloids

Nat Chem. 2014 Apr;6(4):303-9. doi: 10.1038/nchem.1894. Epub 2014 Mar 16.


Enzymes fold into unique three-dimensional structures, which underlie their remarkable catalytic properties. The requirement to adopt a stable, folded conformation is likely to contribute to their relatively large size (>10,000 Da). However, much shorter peptides can achieve well-defined conformations through the formation of amyloid fibrils. To test whether short amyloid-forming peptides might in fact be capable of enzyme-like catalysis, we designed a series of seven-residue peptides that act as Zn(2+)-dependent esterases. Zn(2+) helps stabilize the fibril formation, while also acting as a cofactor to catalyse acyl ester hydrolysis. These results indicate that prion-like fibrils are able to not only catalyse their own formation, but they can also catalyse chemical reactions. Thus, they might have served as intermediates in the evolution of modern-day enzymes. These results also have implications for the design of self-assembling nanostructured catalysts including ones containing a variety of biological and non-biological metal ions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amyloid / chemical synthesis*
  • Carbonic Anhydrases / chemistry
  • Catalysis
  • Humans
  • Hydrolysis
  • Microscopy, Electron, Transmission
  • Peptides / chemistry*
  • Protein Conformation
  • Zinc / chemistry


  • Amyloid
  • Peptides
  • Carbonic Anhydrases
  • Zinc