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dc.contributor.authorCain, Stuart A
dc.contributor.authorBaldock, Clair
dc.contributor.authorGallagher, John T
dc.contributor.authorMorgan, Amanda
dc.contributor.authorBax, Daniel V
dc.contributor.authorWeiss, Anthony S
dc.contributor.authorShuttleworth, C Adrian
dc.contributor.authorKielty, Cay M
dc.date.accessioned2009-07-24T15:36:44Z
dc.date.available2009-07-24T15:36:44Z
dc.date.issued2005-08-26
dc.identifier.citationFibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly. 2005, 280 (34):30526-37 J. Biol. Chem.en
dc.identifier.issn0021-9258
dc.identifier.pmid15980072
dc.identifier.doi10.1074/jbc.M501390200
dc.identifier.urihttp://hdl.handle.net/10541/75637
dc.description.abstractFibrillin-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.isoenen
dc.subject.meshAnimals
dc.subject.meshBiotin
dc.subject.meshBiotinylation
dc.subject.meshCalcium
dc.subject.meshCarbohydrate Sequence
dc.subject.meshContractile Proteins
dc.subject.meshDatabases, Protein
dc.subject.meshEdetic Acid
dc.subject.meshExons
dc.subject.meshExtracellular Matrix Proteins
dc.subject.meshGlycosaminoglycans
dc.subject.meshGlycosylation
dc.subject.meshHeparin
dc.subject.meshHeparitin Sulfate
dc.subject.meshHumans
dc.subject.meshKinetics
dc.subject.meshMicrofilament Proteins
dc.subject.meshModels, Chemical
dc.subject.meshModels, Molecular
dc.subject.meshMolecular Sequence Data
dc.subject.meshMonosaccharides
dc.subject.meshOligosaccharides
dc.subject.meshProtein Binding
dc.subject.meshProtein Structure, Tertiary
dc.subject.meshRecombinant Proteins
dc.subject.meshSwine
dc.subject.meshTime Factors
dc.subject.meshTropoelastin
dc.titleFibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly.en
dc.typeArticleen
dc.contributor.departmentWellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.en
dc.identifier.journalThe Journal of Biological Chemistryen
html.description.abstractFibrillin-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.


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