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Basic Amino Acid Residues of Human Eosinophil Derived Neurotoxin Essential for Glycosaminoglycan Binding
Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 300, Taiwan
Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA
Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan
Stem Cell and Translational Cancer Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan
Department of Medical Science, National Tsing Hua University, Hsinchu 300, Taiwan
* Author to whom correspondence should be addressed.
Received: 15 August 2013; in revised form: 6 September 2013 / Accepted: 11 September 2013 / Published: 16 September 2013
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
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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.
Hung T-J, Chang W-T, Tomiya N, Lee Y-C, Chang H-T, Chen C-J, Kuo P-H, Fan T-C, Chang MD-T. Basic Amino Acid Residues of Human Eosinophil Derived Neurotoxin Essential for Glycosaminoglycan Binding. International Journal of Molecular Sciences. 2013; 14(9):19067-19085.
Hung, Ta-Jen; Chang, Wei-Tang; Tomiya, Noboru; Lee, Yuan-Chuan; Chang, Hao-Teng; Chen, Chien-Jung; Kuo, Ping-Hsueh; Fan, Tan-chi; Chang, Margaret D.-T. 2013. "Basic Amino Acid Residues of Human Eosinophil Derived Neurotoxin Essential for Glycosaminoglycan Binding." Int. J. Mol. Sci. 14, no. 9: 19067-19085.