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TitleAllosteric amyloid catalysis by coiled coil fibrils.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 5071, Year 2025
Publish dateMay 31, 2025
AuthorsSisira Mambram Kunnath / Elad Arad / Ran Zalk / Itamar Kass / Anat Shahar / Albert Batushansky / Hanna Rapaport / Raz Jelinek /
PubMed AbstractAmyloid-mediated catalysis of key biological reactions has recently attracted significant interest as this phenomenon may portend new functions for physiological and synthetic amyloid proteins. Here, ...Amyloid-mediated catalysis of key biological reactions has recently attracted significant interest as this phenomenon may portend new functions for physiological and synthetic amyloid proteins. Here, we report an allosteric mechanism of catalytic amyloids, mediated via an unconventional coiled-coil fibril organization, facilitating hydrolysis of β-lactam antibiotics. Specifically, the hydrolysis reaction was catalyzed by a fibrillar peptide comprising alternating lysine/phenylalanine β-sheet-forming sequence. Analysis of peptide variants, simulations, and cryogenic electron microscopy reveal that the β-lactam molecules attach electrostatically to the lysine sidechains on the fibrils' surfaces, generating a double-coiled fibril structure in which the anchored β-lactam molecules are nestled within twisted fibril strands. This organization facilitates the allosteric catalytic process in which hydrolytic β-lactam ring opening is induced via nucleophilic attacks by the lysine sidechains degradation. The allosteric catalytic activity of the phenylalanine/lysine amyloid fibrils highlights the functional versatility of amyloid fibrils and their potential applications in human health and environmental biotechnology.
External linksNat Commun / PubMed:40450012 / PubMed Central
MethodsEM (helical sym.)
Resolution5.0 Å
Structure data

53305

9r7e

EMDB-53305, PDB-9r7e:
Cryo-EM Structure of catalytic amyloids
Method: EM (helical sym.) / Resolution: 5.0 Å

Chemicals

ChemComp-NEF:
Nitrocefin - open form

Source
  • anaeramoeba ignava (eukaryote)
KeywordsPROTEIN FIBRIL / Allosteric amyloid coiled-coil fibrils

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