Elucidation of the structural features of heparan sulfate important for interaction with the Hep-2 domain of fibronectin.

2.50
Hdl Handle:
http://hdl.handle.net/10541/90037
Title:
Elucidation of the structural features of heparan sulfate important for interaction with the Hep-2 domain of fibronectin.
Authors:
Lyon, Malcolm; Rushton, Graham; Askari, Janet A; Humphries, Martin J; Gallagher, John T
Abstract:
The interaction of fibronectin with cell surface heparan sulfate proteoglycans is important biologically in inducing reorganization of the cytoskeleton and the assembly of focal adhesions. The major heparan sulfate-binding site in fibronectin, which is also implicated in these morphological events, is the COOH-terminal Hep-2 domain. We describe the first extensive study of the structural determinants required for the interaction between heparan sulfate/heparin and Hep-2. It is clear that, in heparan sulfate, there is a very prominent role for N-sulfate groups, as opposed to a relatively small apparent contribution from carboxyl groups. Furthermore, a minimal octasaccharide binding sequence appeared to contain at least two 2-O-sulfated iduronate residues, but no 6-O-sulfate groups. However, affinity was enhanced by the presence of 6-O-sulfates, and the interaction with Hep-2 also increased progressively with oligosaccharide size up to a maximum length of a tetradecasaccharide. This overall specificity is compatible with recent information on the structure of Hep-2 (Sharma, A., Askari, J. A., Humphries, M. J., Jones, E. Y., and Stuart, D. I. (1999) EMBO J. 18, 1468-1479) in which two separate, positively charged clusters, involving up to 11 basic amino acid residues (mostly arginines with their preferential ability to co-ordinate sulfate groups), could form a single extended binding site.
Affiliation:
Cancer Research Campaign Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom. mlyon@picr.man.ac.uk
Citation:
Elucidation of the structural features of heparan sulfate important for interaction with the Hep-2 domain of fibronectin. 2000, 275 (7):4599-606 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
18-Feb-2000
URI:
http://hdl.handle.net/10541/90037
PubMed ID:
10671486
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLyon, Malcolmen
dc.contributor.authorRushton, Grahamen
dc.contributor.authorAskari, Janet Aen
dc.contributor.authorHumphries, Martin Jen
dc.contributor.authorGallagher, John Ten
dc.date.accessioned2010-01-19T16:39:37Z-
dc.date.available2010-01-19T16:39:37Z-
dc.date.issued2000-02-18-
dc.identifier.citationElucidation of the structural features of heparan sulfate important for interaction with the Hep-2 domain of fibronectin. 2000, 275 (7):4599-606 J. Biol. Chem.en
dc.identifier.issn0021-9258-
dc.identifier.pmid10671486-
dc.identifier.urihttp://hdl.handle.net/10541/90037-
dc.description.abstractThe interaction of fibronectin with cell surface heparan sulfate proteoglycans is important biologically in inducing reorganization of the cytoskeleton and the assembly of focal adhesions. The major heparan sulfate-binding site in fibronectin, which is also implicated in these morphological events, is the COOH-terminal Hep-2 domain. We describe the first extensive study of the structural determinants required for the interaction between heparan sulfate/heparin and Hep-2. It is clear that, in heparan sulfate, there is a very prominent role for N-sulfate groups, as opposed to a relatively small apparent contribution from carboxyl groups. Furthermore, a minimal octasaccharide binding sequence appeared to contain at least two 2-O-sulfated iduronate residues, but no 6-O-sulfate groups. However, affinity was enhanced by the presence of 6-O-sulfates, and the interaction with Hep-2 also increased progressively with oligosaccharide size up to a maximum length of a tetradecasaccharide. This overall specificity is compatible with recent information on the structure of Hep-2 (Sharma, A., Askari, J. A., Humphries, M. J., Jones, E. Y., and Stuart, D. I. (1999) EMBO J. 18, 1468-1479) in which two separate, positively charged clusters, involving up to 11 basic amino acid residues (mostly arginines with their preferential ability to co-ordinate sulfate groups), could form a single extended binding site.en
dc.language.isoenen
dc.subject.mesh3T3 Cells-
dc.subject.meshAnimals-
dc.subject.meshChromatography, Affinity-
dc.subject.meshChromatography, High Pressure Liquid-
dc.subject.meshChromatography, Ion Exchange-
dc.subject.meshFibronectins-
dc.subject.meshGlycosaminoglycans-
dc.subject.meshHeparitin Sulfate-
dc.subject.meshMice-
dc.subject.meshMolecular Structure-
dc.titleElucidation of the structural features of heparan sulfate important for interaction with the Hep-2 domain of fibronectin.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Department of Medical Oncology, University of Manchester, Christie Hospital NHS Trust, Manchester M20 4BX, United Kingdom. mlyon@picr.man.ac.uken
dc.identifier.journalThe Journal of Biological Chemistryen
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