The role of the disulfide bond in the interaction of islet amyloid polypeptide with membranes

Khemtémourian, L., Engel, M.F.M., Kruijtzer, J.A.W., Höppener, J.W.M., Liskamp, R.M.J. and Killian, J.A. (2010) The role of the disulfide bond in the interaction of islet amyloid polypeptide with membranes. European Biophysics Journal with Biophysics Letters, 39(9), pp. 1359-1364. (doi:10.1007/s00249-009-0572-4)

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Abstract

Human islet amyloid polypeptide (hIAPP) forms amyloid fibrils in pancreatic islets of patients with type 2 diabetes mellitus. It has been suggested that the N-terminal part, which contains a conserved intramolecular disulfide bond between residues 2 and 7, interacts with membranes, ultimately leading to membrane damage and β-cell death. Here, we used variants of the hIAPP1–19 fragment and model membranes of phosphatidylcholine and phosphatidylserine (7:3, molar ratio) to examine the role of this disulfide in membrane interactions. We found that the disulfide bond has a minor effect on membrane insertion properties and peptide conformational behavior, as studied by monolayer techniques, 2H NMR, ThT-fluorescence, membrane leakage, and CD spectroscopy. The results suggest that the disulfide bond does not play a significant role in hIAPP–membrane interactions. Hence, the fact that this bond is conserved is most likely related exclusively to the biological activity of IAPP as a hormone.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liskamp, Professor Robert
Authors: Khemtémourian, L., Engel, M.F.M., Kruijtzer, J.A.W., Höppener, J.W.M., Liskamp, R.M.J., and Killian, J.A.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:European Biophysics Journal with Biophysics Letters
Publisher:Springer-Verlag
ISSN:0175-7571
ISSN (Online):1432-1017
Copyright Holders:Copyright © 2010 The Authors
First Published:First published in European Biophysics Journal with Biophysics Letters 39(9):1359-1364
Publisher Policy:Reproduced under a Creative Commons License

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