Molecular basis of elastic fiber formation: Critical interactions and a tropoelastin-fibrillin-1 cross-link

Matthew J. Rock, Stuart A. Cain, Lyle J. Freeman, Amanda Morgan, Kieran Mellody, Andrew Marson, C. Adrian Shuttleworth, Anthony S. Weiss, Cay M. Kielty

    Research output: Contribution to journalArticlepeer-review


    We have investigated the molecular basis of elastic fiber formation on fibrillin microfibrils. Binding assays revealed high affinity calcium-independent binding of two overlapping fibrillin-1 fragments (encoded by central exons 18-25 and 24-30) to tropoelastin, which, in microfibrils, map to an exposed "arms" feature adjacent to the beads. A further binding site within an adjacent fragment (encoded by exons 9-17) was within an eight-cysteine motif designated TB2 (encoded by exons 16 and 17). Binding to TB2 was ablated by the presence of N-terminal domains (encoded by exons 1-8) and reduced after deleting the proline-rich region. A novel transglutaminase cross-link between tropoelastin and fibrillin-1 fragment (encoded by exons 9-17) was localized by mass spectrometry to a sequence encoded by exon 17. The high affinity binding and cross-linking of tropoelastin to a central fibrillin-1 sequence confirm that this association is fundamental to elastic fiber formation. Microfibril-associated glycoprotein-1 showed calcium-dependent binding of moderate affinity to fibrillin-1 N-terminal fragment (encoded by exons 1-8), which localize to the beads. Microfibril-associated glycoprotein-1 thus contributes to microfibril organization but may also form secondary interactions with adjacent microfibril-bound tropoelastin.
    Original languageEnglish
    Pages (from-to)23748-23758
    Number of pages10
    JournalJournal of Biological Chemistry
    Issue number22
    Publication statusPublished - 28 May 2004


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