title: Short peptides self-assemble to produce catalytic amyloids.
abstract: 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.
authors.affiliation: 1] Department of Chemistry, Syracuse University, Syracuse, New York 13244, USA [2].
authors.forename: Caroline M
authors.initials: CM
authors.lastname: Rufo
authors.affiliation: 1] Department of Chemistry, Syracuse University, Syracuse, New York 13244, USA [2].
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Moroz
authors.affiliation: 1] Department of Chemistry, Syracuse University, Syracuse, New York 13244, USA [2].
authors.forename: Olesia V
authors.initials: OV
authors.lastname: Moroz
authors.affiliation: Institute for Neurodegenerative Diseases and Department of Neurology, University of California - San Francisco, San Francisco, California 94143, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Stöhr
authors.affiliation: Department of Chemistry, Syracuse University, Syracuse, New York 13244, USA.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Smith
authors.affiliation: Department of Pharmaceutical Chemistry, University of California - San Francisco, Francisco, California 94158, USA.
authors.forename: Xiaozhen
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutical Chemistry, University of California - San Francisco, Francisco, California 94158, USA.
authors.forename: William F
authors.initials: WF
authors.lastname: DeGrado
authors.affiliation: Department of Chemistry, Syracuse University, Syracuse, New York 13244, USA.
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Korendovych
mesh_terms: D000682:Amyloid / Q000138:chemical synthesis*; D002256:Carbonic Anhydrases / Q000737:chemistry; D002384:Catalysis; D006801:Humans; D006868:Hydrolysis; D046529:Microscopy, Electron, Transmission; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D015032:Zinc / Q000737:chemistry
chemical_list: D000682:Amyloid; D010455:Peptides; D002256:Carbonic Anhydrases; D015032:Zinc