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

International Journal of Molecular Sciences

Ta-Jen Hung¹  Wei-Tang Chang¹  Noboru Tomiya³  Yuan-Chuan Lee¹  Hao-Teng Chang⁴  Chien-Jung Chen¹  Ping-Hsueh Kuo¹  Tan-chi Fan² 

[1] Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu 300, Taiwan; E-Mails:;Stem Cell and Translational Cancer Research Center, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan; E-Mail:;Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA; E-Mail:;Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan; E-Mail:

关键词: eosinophil derived neurotoxin;    heparin;    glycosaminoglycan;    heparin binding region;   

DOI  :  10.3390/ijms140919067

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland