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Probing amylin fibrillation at an early stage via a tetracysteine-recognising fluorophore

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Title: Probing amylin fibrillation at an early stage via a tetracysteine-recognising fluorophore
Authors: Wang, C
Lin, Y
Hsu, C
Amdursky, N
Spicer, C
Stevens, MM
Item Type: Journal Article
Abstract: Amyloid fibrillation is a nucleation-dependent process known be involved in the development of more than 20 progressive and chronic diseases. The detection of amyloid formation at the nucleation stage can greatly advance early diagnoses and treatment of diseases. In this work, we developed a new assay for the early detection of amylin fibrillation using the biarsenical dye 4,5-bis(1,3,2-dithiarsolan-2-yl)fluorescein (FlAsH), which could recognise tetracysteine motifs and transform from non-fluorescent form into strongly fluorescent complexes. Due to the close proximity of two cysteine residues within the hydrophilic domain of amylin, a non-contiguous tetracysteine motif can form upon amylin dimerisation or oligomerisation, which can be recognised by FlAsH and emit strong fluorescence. This enables us to report the nucleation-growth process of amylin without modification of the protein sequence. We showed that the use of this assay not only allowed the tracking of initial nucleation events, but also enabled imaging of amyloid fibrils and investigation of the effects of amyloid inhibitor/modulator toward amylin fibrillation.
Issue Date: 17-May-2017
Date of Acceptance: 8-May-2017
URI: http://hdl.handle.net/10044/1/48483
DOI: https://dx.doi.org/10.1016/j.talanta.2017.05.015
ISSN: 1873-3573
Publisher: Elsevier
Start Page: 44
End Page: 50
Journal / Book Title: Talanta
Volume: 173
Copyright Statement: © 2017 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
Sponsor/Funder: Engineering & Physical Science Research Council (E
Engineering & Physical Science Research Council (EPSRC)
Commission of the European Communities
Commission of the European Communities
Funder's Grant Number: EP/K031953/1
EP/K020641/1
ERC-2013-CoG-616417
PIEF-GA-2013-623123
Keywords: Amylin
Amyloid inhibitor
Early detection
Fibrillation
FlAsH
Glycosaminoglycan
Analytical Chemistry
0301 Analytical Chemistry
0399 Other Chemical Sciences
Publication Status: Published
Appears in Collections:Faculty of Engineering
Materials
Faculty of Natural Sciences



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