Basic amino acid residues of human eosinophil derived neurotoxin essential for glycosaminoglycan binding.

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.
Authors	Ta-Jen Hung, Wei-Tang Chang, Noboru Tomiya, Yuan-Chuan Lee, Hao-Teng Chang, Chien-Jung Chen, Ping-Hsueh Kuo, Tan-chi Fan, Margaret Dah-Tsyr Chang
Journal	International journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 9 Pg. 19067-85 (Sep 16 2013) ISSN: 1422-0067 [Electronic] Switzerland
PMID	24065103 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Amino Acids, Basic Glycosaminoglycans Maltose-Binding Proteins Heparin Eosinophil-Derived Neurotoxin
Topics	Amino Acid Sequence Amino Acids, Basic (chemistry, metabolism) Animals Binding Sites CHO Cells Cell Line Cricetinae Cricetulus Eosinophil-Derived Neurotoxin (chemistry, genetics, metabolism) Eosinophils (metabolism) Glycosaminoglycans (metabolism) Heparin (metabolism) Humans Maltose-Binding Proteins (genetics, metabolism) Molecular Docking Simulation Protein Binding Protein Structure, Tertiary

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