The membrane-active amphibian peptide caerin 1.8 inhibits fibril formation of amyloid β1-42

Yanqin Liu; Tianfang Wang; Antonio N Calabrese; John A Carver; Scott F Cummins; John H Bowie

doi:10.1016/j.peptides.2015.08.004

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The membrane-active amphibian peptide caerin 1.8 inhibits fibril formation of amyloid β1-42

Journal article

Open access

Peer reviewed

The membrane-active amphibian peptide caerin 1.8 inhibits fibril formation of amyloid β1-42

Yanqin Liu, Tianfang Wang, Antonio N Calabrese, John A Carver, Scott F Cummins and John H Bowie

Peptides, Vol.73, pp.1-6

2015

DOI: https://doi.org/10.1016/j.peptides.2015.08.004

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Abstract

Alzheimer's disease

Amyloid beta 1-42 (Aβ42)

Amyloid fibrils

Caerin 1.8, an Aβ42 fibrilisation inhibitor

MALDI mass spectrometry: 1:1 adduct

[Aβ42/caerin 1.8]H+

MD simulation of 1:1 adduct in water

The amphibian host-defense peptide caerin 1.8 [1GLFKVLGSV10AKHLLPHVVP20VIAEKL(NH2)] inhibits fibril formation of amyloid β 1-42 [1DAEFRHDSG10YEVHHQKLVF20FAEDVGSNKG30AIIGLMVGGV40VIA] [Aβ42] (the major precursor of the extracellular fibrillar deposits of Alzheimer's disease). Some truncated forms of caerin 1.8 also inhibit fibril formation of Aβ42. For example, caerin 1.8 (1-13) [1GLFKVLGSV10AKHL(NH2) and caerin 1.8 (22-25) [KVLGSV10AKHLLPHVVP20VIAEKL(NH2)] show 85% and 75% respectively of the inhibition activity of the parent caerin 1.8. The synthetic peptide KLVFFKKKKKK is a known inhibitor of Aβ42 fibril formation, and was used as a standard in this study. Caerin 1.8 is the more effective fibril inhibitor. IC50 values (± 15%) are caerin 1.8 (75 μM) and KLVFFKKKKKK (370 μM). MALDI mass spectrometry shows the presence of a small peak corresponding to a protonated 1:1 adduct [caerin 1.8/Aβ42]H+. Molecular dynamics simulation suggests that both hydrogen bonding and hydrophobic interactions between Aβ42 and caerin 1.8 facilitate the formation of a 1:1 complex in water. Fibril formation from Aβ42 has been proposed to be based around the 16KLVF20F region of Aβ42; this region in the 1:1 complex is partially blocked from attachment of a further molecule of Aβ42.

Details

Title: The membrane-active amphibian peptide caerin 1.8 inhibits fibril formation of amyloid β1-42
Authors: Yanqin Liu (Author) - University of Adelaide
Tianfang Wang (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and Engineering
Antonio N Calabrese (Author) - University of Adelaide
John A Carver (Author) - Australian National University
Scott F Cummins (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and Engineering
John H Bowie (Author) - University of Adelaide
Publication details: Peptides, Vol.73, pp.1-6
Publisher: Elsevier Inc.
Date published: 2015
DOI: 10.1016/j.peptides.2015.08.004
ISSN: 0196-9781
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99450102702621
Output Type: Journal article

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4 Times Cited - Web of Science

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Collaboration types: Domestic collaboration
Web Of Science research areas: Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy