Molecular basis of elastic fiber formation. Critical interactions and a tropoelastin-fibrillin-1 cross-link.
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.[1]References
- Molecular basis of elastic fiber formation. Critical interactions and a tropoelastin-fibrillin-1 cross-link. Rock, M.J., Cain, S.A., Freeman, L.J., Morgan, A., Mellody, K., Marson, A., Shuttleworth, C.A., Weiss, A.S., Kielty, C.M. J. Biol. Chem. (2004) [Pubmed]
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