Amyloid Aggregation and Membrane Activity of the Antimicrobial Peptide Uperin 3.5

Lisandra L. Martin, Clemens Kubeil, Stefania Piantavigna, Tarun Tikkoo, Nicholas P. Gray, Torsten John, Antonio N. Calabrese, Yanqin Liu, Yuning Hong, Mohammed A. Hossain, Nitin Patil, Bernd Abel, Ralf Hoffmann, John H. Bowie, John A. Carver

Research output: Contribution to journalArticle

Abstract

Amyloid fibrils are highly ordered, β-sheet rich forms of aggregated peptides and proteins that are associated with a variety of pathological human disorders, including Alzheimer's and Parkinson's diseases. Amyloid fibril-forming peptides may be functionally related to antimicrobial peptides, despite differing significantly in sequence and structure. Specifically, their interaction with lipid membranes has mechanistic similarities. The 17-amino acid peptide uperin 3.5 (U3.5) from an Australian amphibian is antimicrobial and amyloidogenic. Using a quartz crystal microbalance, we investigated the interaction of U3.5 with artificial membranes and found that (i) the membrane interaction of U3.5 is independent of the peptide's aggregation state, (ii) the presence of cholesterol in the membrane dramatically alters peptide–membrane interaction leading to a transmembrane pore-like arrangement of U3.5, and (iii) electrostatic interaction is important for the membrane activity of U3.5 whereby removal of the positive charge at position 7 of U3.5 enhanced its fibrillar aggregation and ablated its membrane interaction, i.e. there is an inverse relationship between the antimicrobial and amyloidogenic properties of U3.5.
LanguageEnglish
Number of pages9
JournalBiopolymers
DOIs
StateAccepted/In press - 23 Feb 2018

Keywords

  • aggregation
  • amyloid
  • antimicrobial
  • membrane disruption
  • peptides
  • quartz crystal microbalance

Cite this

Martin, Lisandra L. ; Kubeil, Clemens ; Piantavigna, Stefania ; Tikkoo, Tarun ; Gray, Nicholas P. ; John, Torsten ; Calabrese, Antonio N. ; Liu, Yanqin ; Hong, Yuning ; Hossain, Mohammed A. ; Patil, Nitin ; Abel, Bernd ; Hoffmann, Ralf ; Bowie, John H. ; Carver, John A./ Amyloid Aggregation and Membrane Activity of the Antimicrobial Peptide Uperin 3.5. In: Biopolymers. 2018
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author = "Martin, {Lisandra L.} and Clemens Kubeil and Stefania Piantavigna and Tarun Tikkoo and Gray, {Nicholas P.} and Torsten John and Calabrese, {Antonio N.} and Yanqin Liu and Yuning Hong and Hossain, {Mohammed A.} and Nitin Patil and Bernd Abel and Ralf Hoffmann and Bowie, {John H.} and Carver, {John A.}",
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Martin, LL, Kubeil, C, Piantavigna, S, Tikkoo, T, Gray, NP, John, T, Calabrese, AN, Liu, Y, Hong, Y, Hossain, MA, Patil, N, Abel, B, Hoffmann, R, Bowie, JH & Carver, JA 2018, 'Amyloid Aggregation and Membrane Activity of the Antimicrobial Peptide Uperin 3.5' Biopolymers. DOI: 10.1002/pep2.24052

Amyloid Aggregation and Membrane Activity of the Antimicrobial Peptide Uperin 3.5. / Martin, Lisandra L.; Kubeil, Clemens; Piantavigna, Stefania; Tikkoo, Tarun; Gray, Nicholas P.; John, Torsten; Calabrese, Antonio N.; Liu, Yanqin; Hong, Yuning; Hossain, Mohammed A.; Patil, Nitin; Abel, Bernd ; Hoffmann, Ralf; Bowie, John H.; Carver, John A.

In: Biopolymers, 23.02.2018.

Research output: Contribution to journalArticle

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AU - Martin,Lisandra L.

AU - Kubeil,Clemens

AU - Piantavigna,Stefania

AU - Tikkoo,Tarun

AU - Gray,Nicholas P.

AU - John,Torsten

AU - Calabrese,Antonio N.

AU - Liu,Yanqin

AU - Hong,Yuning

AU - Hossain,Mohammed A.

AU - Patil,Nitin

AU - Abel,Bernd

AU - Hoffmann,Ralf

AU - Bowie,John H.

AU - Carver,John A.

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N2 - Amyloid fibrils are highly ordered, β-sheet rich forms of aggregated peptides and proteins that are associated with a variety of pathological human disorders, including Alzheimer's and Parkinson's diseases. Amyloid fibril-forming peptides may be functionally related to antimicrobial peptides, despite differing significantly in sequence and structure. Specifically, their interaction with lipid membranes has mechanistic similarities. The 17-amino acid peptide uperin 3.5 (U3.5) from an Australian amphibian is antimicrobial and amyloidogenic. Using a quartz crystal microbalance, we investigated the interaction of U3.5 with artificial membranes and found that (i) the membrane interaction of U3.5 is independent of the peptide's aggregation state, (ii) the presence of cholesterol in the membrane dramatically alters peptide–membrane interaction leading to a transmembrane pore-like arrangement of U3.5, and (iii) electrostatic interaction is important for the membrane activity of U3.5 whereby removal of the positive charge at position 7 of U3.5 enhanced its fibrillar aggregation and ablated its membrane interaction, i.e. there is an inverse relationship between the antimicrobial and amyloidogenic properties of U3.5.

AB - Amyloid fibrils are highly ordered, β-sheet rich forms of aggregated peptides and proteins that are associated with a variety of pathological human disorders, including Alzheimer's and Parkinson's diseases. Amyloid fibril-forming peptides may be functionally related to antimicrobial peptides, despite differing significantly in sequence and structure. Specifically, their interaction with lipid membranes has mechanistic similarities. The 17-amino acid peptide uperin 3.5 (U3.5) from an Australian amphibian is antimicrobial and amyloidogenic. Using a quartz crystal microbalance, we investigated the interaction of U3.5 with artificial membranes and found that (i) the membrane interaction of U3.5 is independent of the peptide's aggregation state, (ii) the presence of cholesterol in the membrane dramatically alters peptide–membrane interaction leading to a transmembrane pore-like arrangement of U3.5, and (iii) electrostatic interaction is important for the membrane activity of U3.5 whereby removal of the positive charge at position 7 of U3.5 enhanced its fibrillar aggregation and ablated its membrane interaction, i.e. there is an inverse relationship between the antimicrobial and amyloidogenic properties of U3.5.

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KW - amyloid

KW - antimicrobial

KW - membrane disruption

KW - peptides

KW - quartz crystal microbalance

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SN - 0006-3525

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