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Kinetic and structural studies on interactions between heparin or heparan sulfate and proteins of the hedgehog signaling pathway.

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.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Zhang F,McLellan JS,Ayala AM,Leahy DJ,Linhardt RJ

doi

10.1021/bi6025424

subject

Has Abstract

pub_date

2007-04-03 00:00:00

pages

3933-41

issue

13

eissn

0006-2960

issn

1520-4995

journal_volume

46

pub_type

杂志文章

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