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

Stuart A. Cain, Clair Baldock, John Gallagher, Amanda Morgan, Daniel V. Bax, Anthony S. Weiss, C. Adrian Shuttleworth, Cay M. Kielty

    Research output: Contribution to journalArticlepeer-review


    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. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
    Original languageEnglish
    Pages (from-to)30526-30537
    Number of pages11
    JournalJournal of Biological Chemistry
    Issue number34
    Publication statusPublished - 26 Aug 2005


    • Animals
    • chemistry: Biotin
    • Biotinylation
    • metabolism: Calcium
    • Carbohydrate Sequence
    • chemistry: Contractile Proteins
    • Databases, Protein
    • chemistry: Edetic Acid
    • Exons
    • chemistry: Extracellular Matrix Proteins
    • chemistry: Glycosaminoglycans
    • Glycosylation
    • chemistry: Heparin
    • chemistry: Heparitin Sulfate
    • Humans
    • Kinetics
    • chemistry: Microfilament Proteins
    • Models, Chemical
    • Models, Molecular
    • Molecular Sequence Data
    • chemistry: Monosaccharides
    • chemistry: Oligosaccharides
    • Protein Binding
    • Protein Structure, Tertiary
    • chemistry: Recombinant Proteins
    • Research Support, Non-U.S. Gov't
    • Swine
    • Time Factors
    • chemistry: Tropoelastin


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