Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly.

2.50
Hdl Handle:
http://hdl.handle.net/10541/75637
Title:
Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly.
Authors:
Cain, Stuart A; Baldock, Clair; Gallagher, John T; Morgan, Amanda; Bax, Daniel V; Weiss, Anthony S; Shuttleworth, C Adrian; Kielty, Cay M
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.
Affiliation:
Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Citation:
Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly. 2005, 280 (34):30526-37 J. Biol. Chem.
Journal:
The Journal of Biological Chemistry
Issue Date:
26-Aug-2005
URI:
http://hdl.handle.net/10541/75637
DOI:
10.1074/jbc.M501390200
PubMed ID:
15980072
Type:
Article
Language:
en
ISSN:
0021-9258
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
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.en
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

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