Journal Article

PUBDB-2025-00584

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural and Functional Versatility of the Amyloidogenic Non-Amidated Variant of the Antimicrobial Peptide Citropin 1.3

Strati, F.Extern*CSSB* ; Pigozzi Cali, M.CSSB*DESY* ; Bloch, Y.Extern*EMBL* ; Mostafavi, S.CSSB*EMBL* ; Monistrol, J.CSSB*DESY* ; Golubev, A.CSSB*DESY* ; Rayan, B.Extern*EMBL* ; Gustavsson, E.CSSB*DESY* ; Landau, M. (Corresponding author)CSSB*EMBL*DESY*

2025
Wiley-VCH Weinheim

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Please use a persistent id in citations: doi:10.1002/advs.202503997  doi:10.3204/PUBDB-2025-00584

Abstract: Citropin 1.3 is an antimicrobial peptide produced by the amphibian Litoria citropa (Southern bell frog), which self-aggregates into distinct fibrillar structures, however, the function of the fibrils remains unclear and largely unexplored. In this study, the structural and functional properties of citropin 1.3 were investigated using cryogenic electron microscopy and fluorescence microscopy in the presence of membrane and cell models, and with X-ray crystallography. Canonical amyloids, multilayered nanotubes, and a novel mixed fibril were observed. Experiments with negatively charged giant unilamellar vesicles revealed that the peptide facilitates membrane fusion while simultaneously undergoing phase separation in the presence of phospholipids. In presence of mammalian cells, citropin 1.3 permeabilizes membranes, leading to cell death, and over time, colocalizes with genetic material. Overall, this work provides new insights into the structural dynamics of the amyloidogenic antimicrobial peptide citropin 1.3 and its interactions with different systems.

Note: Cure Alzheimer's Fund, the Forschungskooperation Niedersachsen – Israel, Volkswagenstiftung, No: 76251-4659/2022 (ZN 4042)

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Contributing Institute(s):

1. FPF Functional Protein Fibrils (CSSB-F)
2. CSSB-EMBL-JK (CSSB-EMBL-JK)
3. EMBL (EMBL)
4. EMBL-User (EMBL-User)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)
3. FuncAmyloid - Structure, Function and Regulation of Antimicrobial and Virulent Amyloids at High-resolution (101087140) (101087140)

Experiment(s):

1. PETRA Beamline P14 (PETRA III)

Appears in the scientific report 2025

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