Kinetic and Structural Studies on Interactions between Heparin/Heparan Sulfate and Proteins of the Hedgehog Signaling Pathway
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Authors
Zhang, Fuming
McLellan, Jason S.
Ayala, Alondra M.
Leahy, Daniel J.
Linhardt, Robert J.
Issue Date
2007-04-03
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Heparan sulfate (HS) proteoglycans (PGs) interact with a number of extracellular signaling proteins, thereby playing an essential role in the regulation of many physiological processes. These interactions are important for both normal signal transduction and regulation of the tissue distribution of signaling molecules. In this study, we use surface plasmon resonance (SPR) to study interactions of HS and structurally related heparin with proteins in the Hedgehog signaling pathway. SPR analysis shows that heparin binds with different affinities to active fragments of the proteins Hedgehog (Hh), Interference Hedgehog (Ihog), Cam-related/Down-regulated by Oncogenes (CDO), and Sonic Hedgehog (Shh). Solution competition studies show that the minimum size of a heparin oligosaccharide capable of interacting with Ihog is larger than a tetrasaccharide and for interacting with Shh is larger than an octasaccharide. In comparison with heparin, Ihog and Shh exhibited a lower affinity for HS than for heparin, and CDO and Hh exhibit negligible binding to HS. This study clearly demonstrates Shh and Ihog are heparin and HS binding proteins and that both molecules preferentially bind heparin or HS having a high level of sulfation.
Description
Biochemistry, 46, 3933-3941
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
Kinetic and Structural Studies on Interactions between Heparin/Heparan Sulfate and Proteins of the Hedgehog Signaling Pathway, F. Zhang, J. S. McLellan, A. M. A. Jiménez, D. J. Leahy, R. J. Linhardt, Biochemistry, 46, 3933-3941, 2007.
Publisher
American Chemical Society (ACS)
Terms of Use
Journal
Volume
Issue
PubMed ID
DOI
ISSN
62960