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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Life Science / Faculty of Advanced Life Science >
Peer-reviewed Journal Articles, etc >
Structure of Pleiotrophin- and Hepatocyte Growth Factor-binding Sulfated Hexasaccharide Determined by Biochemical and Computational Approaches
| Title: | Structure of Pleiotrophin- and Hepatocyte Growth Factor-binding Sulfated Hexasaccharide Determined by Biochemical and Computational Approaches |
| Authors: | Li, Fuchuan Browse this author | | Nandini, Chilkunda D. Browse this author | | Hattori, Tomohide Browse this author | | Bao, Xingfeng Browse this author | | Murayama, Daisuke Browse this author | | Nakamura, Toshikazu Browse this author | | Fukushima, Nobuhiro Browse this author | | Sugahara, Kazuyuki Browse this author →KAKEN DB |
| Issue Date: | 3-Sep-2010 |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 285 |
| Issue: | 36 |
| Start Page: | 27673 |
| End Page: | 27685 |
| Publisher DOI: | 10.1074/jbc.M110.118703 |
| PMID: | 20584902 |
| Abstract: | Endogenous pleiotrophin and hepatocyte growth factor (HGF) mediate the neurite outgrowth-promoting activity of chondroitin sulfate (CS)/dermatan sulfate (DS) hybrid chains isolated from embryonic pig brain. CS/DS hybrid chains isolated from shark skin have a different disaccharide composition, but also display these activities. In this study, pleiotrophin- and HGF-binding domains in shark skin CS/DS were investigated. A high-affinity CS/DS fraction was isolated using a pleiotrophin-immobilized column. It showed marked neurite outgrowth-promoting activity and strong inhibitory activity against the binding of pleiotrophin to immobilized CS/DS chains from embryonic pig brain. The inhibitory activity was abolished by chondroitinase ABC or B, and partially reduced by chondroitinase AC-I. A pentasulfated hexasaccharide with a novel structure was isolated from the chondroitinase AC-I digest using pleiotrophin-affinity and anion-exchange chromatographies. It displayed a potent inhibitory effect on the binding of HGF to immobilized shark skin CS/DS chains, suggesting that the pleiotrophin- and HGF-binding domains at least partially overlap in the CS/DS chains involved in the neuritogenic activity. Computational chemistry using molecular modeling and calculations of the electrostatic potential of the hexasaccharide and two pleiotrophin-binding octasaccharides previously isolated from CS/DS hybrid chains of embryonic pig brain identified an electronegative zone potentially involved in the molecular recognition of the oligosaccharides by pleiotrophin. Homology modeling of pleiotrophin based on a related midkine protein structure predicted the binding pocket of pleiotrophin for the oligosaccharides and provided new insights into the molecular mechanism of the interactions between the oligosaccharides and pleiotrophin. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/44207 |
| Appears in Collections: | 生命科学院・先端生命科学研究院 (Graduate School of Life Science / Faculty of Advanced Life Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 菅原 一幸
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