Please use this identifier to cite or link to this item:
Title: Structure-function analysis of full-length midkine reveals novel residues important for heparin binding and zebrafish embryogenesis
Authors: Lim, J.
Yao, S.
Graf, M.
Winkler, C. 
Yang, D. 
Keywords: Cancer
Heparin binding
Structure-function relationship
Zebrafish embryo development
Issue Date: 1-May-2013
Source: Lim, J., Yao, S., Graf, M., Winkler, C., Yang, D. (2013-05-01). Structure-function analysis of full-length midkine reveals novel residues important for heparin binding and zebrafish embryogenesis. Biochemical Journal 451 (3) : 407-415. ScholarBank@NUS Repository.
Abstract: Midkine is a heparin-binding di-domain growth factor, implicated in many biological processes as diverse as angiogenesis, neurogenesis and tumorigenesis. Elevated midkine levels reflect poor prognosis for many carcinomas, yet the molecular and cellular mechanisms orchestrating its activity remain unclear. At the present time, the individual structures of isolated half domains of human midkine are known and its functionally active C-terminal half domain remains a popular therapeutic target. In the present study, we determined the structure of full-length zebrafish midkine and show that it interacts with fondaparinux (a synthetic highly sulfated pentasaccharide) and natural heparin through a previously uncharacterized, but highly conserved, hinge region. Mutating six consecutive residues in the conserved hinge to glycine strongly abates heparin binding and midkine embryogenic activity. In contrast with previous in vitro studies, we found that the isolated C-terminal half domain is not active in vivo in embryos. Instead, we have demonstrated that the N-terminal half domain is needed to enhance heparin binding and mediate midkine embryogenic activity surprisingly in both heparin-dependent and -independent manners. Our findings provide new insights into the structural features of full-length midkine relevant for embryogenesis, and unravel additional therapeutic routes targeting the N-terminal half domain and conserved hinge. © 2013 Biochemical Society.
Source Title: Biochemical Journal
ISSN: 02646021
DOI: 10.1042/BJ20121622
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Mar 7, 2018


checked on Jan 29, 2018

Page view(s)

checked on Mar 11, 2018

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.