Fibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly.
AuthorsCain, Stuart A
Gallagher, John T
Bax, Daniel V
Weiss, Anthony S
Shuttleworth, C Adrian
Kielty, Cay M
AffiliationWellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
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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.
CitationFibrillin-1 interactions with heparin. Implications for microfibril and elastic fiber assembly. 2005, 280 (34):30526-37 J. Biol. Chem.
JournalThe Journal of Biological Chemistry
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