Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly.
dc.contributor.author | Cain, Stuart A | |
dc.contributor.author | Baldock, Clair | |
dc.contributor.author | Gallagher, John T | |
dc.contributor.author | Morgan, Amanda | |
dc.contributor.author | Bax, Daniel V | |
dc.contributor.author | Weiss, Anthony S | |
dc.contributor.author | Shuttleworth, C Adrian | |
dc.contributor.author | Kielty, Cay M | |
dc.date.accessioned | 2009-07-24T15:36:44Z | |
dc.date.available | 2009-07-24T15:36:44Z | |
dc.date.issued | 2005-08-26 | |
dc.identifier.citation | Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly. 2005, 280 (34):30526-37 J. Biol. Chem. | en |
dc.identifier.issn | 0021-9258 | |
dc.identifier.pmid | 15980072 | |
dc.identifier.doi | 10.1074/jbc.M501390200 | |
dc.identifier.uri | http://hdl.handle.net/10541/75637 | |
dc.description.abstract | Fibrillin-1 assembly into microfibrils and elastic fiber formation involves interactions with glycosaminoglycans. We have used BIAcore technology to investigate fibrillin-1 interactions with heparin and with heparin saccharides that are analogous to S-domains of heparan sulfate. We have identified four high affinity heparin-binding sites on fibrillin-1, localized three of these sites, and defined their binding kinetics. Heparin binding to the fibrillin-1 N terminus has particularly rapid kinetics. Hyaluronan and chondroitin sulfate did not interact significantly with fibrillin-1. Heparin saccharides with more than 12 monosaccharide units bound strongly to all four fibrillin-1 sites. Heparin did not inhibit fibrillin-1 N- and C-terminal interactions or RGD-dependent cell attachment, but heparin and MAGP-1 competed for binding to the fibrillin-1 N terminus, and heparin and tropoelastin competed for binding to a central fibrillin-1 sequence. By regulating these key interactions, heparin can profoundly influence microfibril and elastic fiber assembly. | |
dc.language.iso | en | en |
dc.subject.mesh | Animals | |
dc.subject.mesh | Biotin | |
dc.subject.mesh | Biotinylation | |
dc.subject.mesh | Calcium | |
dc.subject.mesh | Carbohydrate Sequence | |
dc.subject.mesh | Contractile Proteins | |
dc.subject.mesh | Databases, Protein | |
dc.subject.mesh | Edetic Acid | |
dc.subject.mesh | Exons | |
dc.subject.mesh | Extracellular Matrix Proteins | |
dc.subject.mesh | Glycosaminoglycans | |
dc.subject.mesh | Glycosylation | |
dc.subject.mesh | Heparin | |
dc.subject.mesh | Heparitin Sulfate | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Kinetics | |
dc.subject.mesh | Microfilament Proteins | |
dc.subject.mesh | Models, Chemical | |
dc.subject.mesh | Models, Molecular | |
dc.subject.mesh | Molecular Sequence Data | |
dc.subject.mesh | Monosaccharides | |
dc.subject.mesh | Oligosaccharides | |
dc.subject.mesh | Protein Binding | |
dc.subject.mesh | Protein Structure, Tertiary | |
dc.subject.mesh | Recombinant Proteins | |
dc.subject.mesh | Swine | |
dc.subject.mesh | Time Factors | |
dc.subject.mesh | Tropoelastin | |
dc.title | Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly. | en |
dc.type | Article | en |
dc.contributor.department | Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom. | en |
dc.identifier.journal | The Journal of Biological Chemistry | en |
html.description.abstract | Fibrillin-1 assembly into microfibrils and elastic fiber formation involves interactions with glycosaminoglycans. We have used BIAcore technology to investigate fibrillin-1 interactions with heparin and with heparin saccharides that are analogous to S-domains of heparan sulfate. We have identified four high affinity heparin-binding sites on fibrillin-1, localized three of these sites, and defined their binding kinetics. Heparin binding to the fibrillin-1 N terminus has particularly rapid kinetics. Hyaluronan and chondroitin sulfate did not interact significantly with fibrillin-1. Heparin saccharides with more than 12 monosaccharide units bound strongly to all four fibrillin-1 sites. Heparin did not inhibit fibrillin-1 N- and C-terminal interactions or RGD-dependent cell attachment, but heparin and MAGP-1 competed for binding to the fibrillin-1 N terminus, and heparin and tropoelastin competed for binding to a central fibrillin-1 sequence. By regulating these key interactions, heparin can profoundly influence microfibril and elastic fiber assembly. |