The amyloid fibril-forming properties of the amphibian antimicrobial peptide uperin 3.5

Antonio N. Calabrese, Yanqin Liu, Tianfang Wang, Ian F. Musgrave, Tara L. Pukala, Rico Tabor, Lisa Martin, John A Carver, John H Bowie

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)239-246
Number of pages8
JournalChemBioChem
Volume17
Issue number3
DOIs
Publication statusPublished - 2 Feb 2016

Keywords

  • aggregation
  • amyloid
  • antimicrobial peptides
  • mass spectrometry
  • uperin

Cite this

Calabrese, A. N., Liu, Y., Wang, T., Musgrave, I. F., Pukala, T. L., Tabor, R., ... Bowie, J. H. (2016). The amyloid fibril-forming properties of the amphibian antimicrobial peptide uperin 3.5. ChemBioChem, 17(3), 239-246. https://doi.org/10.1002/cbic.201500518
Calabrese, Antonio N. ; Liu, Yanqin ; Wang, Tianfang ; Musgrave, Ian F. ; Pukala, Tara L. ; Tabor, Rico ; Martin, Lisa ; Carver, John A ; Bowie, John H. / The amyloid fibril-forming properties of the amphibian antimicrobial peptide uperin 3.5. In: ChemBioChem. 2016 ; Vol. 17, No. 3. pp. 239-246.
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Calabrese, AN, Liu, Y, Wang, T, Musgrave, IF, Pukala, TL, Tabor, R, Martin, L, Carver, JA & Bowie, JH 2016, 'The amyloid fibril-forming properties of the amphibian antimicrobial peptide uperin 3.5', ChemBioChem, vol. 17, no. 3, pp. 239-246. https://doi.org/10.1002/cbic.201500518

The amyloid fibril-forming properties of the amphibian antimicrobial peptide uperin 3.5. / Calabrese, Antonio N.; Liu, Yanqin; Wang, Tianfang; Musgrave, Ian F.; Pukala, Tara L.; Tabor, Rico; Martin, Lisa; Carver, John A; Bowie, John H.

In: ChemBioChem, Vol. 17, No. 3, 02.02.2016, p. 239-246.

Research output: Contribution to journalArticleResearchpeer-review

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