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Int. J. Mol. Sci. 2013, 14(9), 19067-19085; doi:10.3390/ijms140919067
Article

Basic Amino Acid Residues of Human Eosinophil Derived Neurotoxin Essential for Glycosaminoglycan Binding

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Received: 15 August 2013 / Revised: 6 September 2013 / Accepted: 11 September 2013 / Published: 16 September 2013
(This article belongs to the collection Proteins and Protein-Ligand Interactions)
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Abstract

Human eosinophil derived neurotoxin (EDN), a granule protein secreted by activated eosinophils, is a biomarker for asthma in children. EDN belongs to the human RNase A superfamily possessing both ribonucleolytic and antiviral activities. EDN interacts with heparin oligosaccharides and heparin sulfate proteoglycans on bronchial epithelial Beas-2B cells. In this study, we demonstrate that the binding of EDN to cells requires cell surface glycosaminoglycans (GAGs), and the binding strength between EDN and GAGs depends on the sulfation levels of GAGs. Furthermore, in silico computer modeling and in vitro binding assays suggest critical roles for the following basic amino acids located within heparin binding regions (HBRs) of EDN 34QRRCKN39 (HBR1), 65NKTRKN70 (HBR2), and 113NRDQRRD119 (HBR3) and in particular Arg35, Arg36, and Arg38 within HBR1, and Arg114 and Arg117 within HBR3. Our data suggest that sulfated GAGs play a major role in EDN binding, which in turn may be related to the cellular effects of EDN.
Keywords: eosinophil derived neurotoxin; heparin; glycosaminoglycan; heparin binding region eosinophil derived neurotoxin; heparin; glycosaminoglycan; heparin binding region
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Hung, T.-J.; Chang, W.-T.; Tomiya, N.; Lee, Y.-C.; Chang, H.-T.; Chen, C.-J.; Kuo, P.-H.; Fan, T.-C.; Chang, M.D.-T. Basic Amino Acid Residues of Human Eosinophil Derived Neurotoxin Essential for Glycosaminoglycan Binding. Int. J. Mol. Sci. 2013, 14, 19067-19085.

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