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Type: Journal article
Title: The amyloid fibril-forming properties of the amphibian antimicrobial peptide uperin 3.5
Author: Calabrese, A.
Liu, Y.
Wang, T.
Musgrave, I.
Pukala, T.
Tabor, R.
Martin, L.
Carver, J.
Bowie, J.
Citation: ChemBioChem: a European journal of chemical biology, 2016; 17(3):239-246
Publisher: Wiley-VCH Verlag GmbH
Issue Date: 2016
ISSN: 1439-4227
Statement of
Antonio N. Calabrese, Yanqin Liu, Tianfang Wang, Ian F. Musgrave, Tara L. Pukala, Rico F. Tabor, Lisandra L. Martin, John A. Carver, John H. Bowie
Abstract: The amphibian skin is a vast resource for bioactive peptides, which form the basis of the animals' innate immune system. Key components of the secretions of the cutaneous glands are antimicrobial peptides (AMPs), which exert their cytotoxic effects often as a result of membrane disruption. It is becoming increasingly evident that there is a link between the mechanism of action of AMPs and amyloidogenic peptides and proteins. In this work, we demonstrate that the broad-spectrum amphibian AMP uperin 3.5, which has a random-coil structure in solution but adopts an α-helical structure in membrane-like environments, forms amyloid fibrils rapidly in solution at neutral pH. These fibrils are cytotoxic to model neuronal cells in a similar fashion to those formed by the proteins implicated in neurodegenerative diseases. The addition of small quantities of 2,2,2-trifluoroethanol accelerates fibril formation by uperin 3.5, and is correlated with a structural stabilisation induced by this co-solvent. Uperin 3.5 fibril formation and the associated cellular toxicity are inhibited by the polyphenol (-)-epigallocatechin-3-gallate (EGCG). Furthermore, EGCG rapidly dissociates fully formed uperin 3.5 fibrils. Ion mobility-mass spectrometry reveals that uperin 3.5 adopts various oligomeric states in solution. Combined, these observations imply that the mechanism of membrane permeability by uperin 3.5 is related to its fibril-forming properties.
Keywords: aggregation
antimicrobial peptides
mass spectrometry
Rights: © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/cbic.201500518
Grant ID: ARC
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