Allosteric amyloid catalysis by coiled coil fibrils

Sisira Mambram Kunnath, Elad Arad, Ran Zalk, Itamar Kass, Anat Shahar, Albert Batushansky, Hanna Rapaport and Raz Jelinek ()
Additional contact information
Sisira Mambram Kunnath: Ilse Katz Institute (IKI) for Nanoscale Science and Technology, Ben-Gurion University of the Negev
Elad Arad: Ilse Katz Institute (IKI) for Nanoscale Science and Technology, Ben-Gurion University of the Negev
Ran Zalk: Ilse Katz Institute (IKI) for Nanoscale Science and Technology, Ben-Gurion University of the Negev
Itamar Kass: Ilse Katz Institute (IKI) for Nanoscale Science and Technology, Ben-Gurion University of the Negev
Anat Shahar: Ilse Katz Institute (IKI) for Nanoscale Science and Technology, Ben-Gurion University of the Negev
Albert Batushansky: Ilse Katz Institute (IKI) for Nanoscale Science and Technology, Ben-Gurion University of the Negev
Hanna Rapaport: Ilse Katz Institute (IKI) for Nanoscale Science and Technology, Ben-Gurion University of the Negev
Raz Jelinek: Ilse Katz Institute (IKI) for Nanoscale Science and Technology, Ben-Gurion University of the Negev

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-60379-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60379-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-60379-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().