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Structural and Functional Versatility of the Amyloidogenic Non‐Amidated Variant of the Antimicrobial Peptide Citropin 1.3

2025/09/28 by Fabio Strati, Mariana P. Cali, Yehudi Bloch +6 · 1 voice · 3 citations
Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · #Antimicrobial Peptides and Activities #RNA and protein synthesis mechanisms #Lipid Membrane Structure and Behavior

paper · doi:10.1002/advs.202503997

Abstract

Citropin 1.3 is an antimicrobial peptide secreted by the amphibian Litoria citropa (Southern bell frog). In this study, the structural and functional properties of its non-amidated form, which self-assembles into distinct fibrillar architectures, are investigated. Using cryogenic electron microscopy, X-ray crystallography, and fluorescence microscopy with model membranes and cells, diverse supramolecular structures, including canonical amyloid fibrils, multilayered nanotubes, and a novel mixed fibril type, are identified. In giant unilamellar vesicles, citropin 1.3 promoted membrane fusion and underwent lipid-induced phase separation. In mammalian cells, it permeabilized membranes, induced cell death, and colocalized with nucleic acids. These findings link antimicrobial activity to amyloid assembly and highlight the peptide's structural plasticity and potential biological functions, offering new insights into amyloid-based antimicrobial mechanisms.

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