| Autor: |
Kieran T. Mellody, C. Adrian Shuttleworth, Lyle J. Freeman, Andrew Marson, Stuart A. Cain, Matthew J. Rock, Amanda Morgan, Cay M. Kielty, Anthony S. Weiss |
| Rok vydání: |
2004 |
| Předmět: |
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| Zdroj: |
Journal of Biological Chemistry. 279:23748-23758 |
| ISSN: |
0021-9258 |
| DOI: |
10.1074/jbc.m400212200 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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