Nanostructure of fibrillin-1 reveals compact conformation of EGF arrays and mechanism for extensibility
| Autor: | Ming Chuan Wang, Richard Berry, Cay M. Kielty, Manfred Roessle, Clair Baldock, Daniel V. Bax, Kieran T. Mellody, J. Louise Haston, J. Günter Grossmann, Veronique Siegler, Tim J Wess, Andrew Marson, Stuart A. Cain |
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| Rok vydání: | 2006 |
| Předmět: |
Models
Molecular Nanostructure Materials science Fibrillin-1 Molecular Conformation Fibrillins Light scattering Fibrillin Microfibrils Image Processing Computer-Assisted Humans Globular Region Multidisciplinary Epidermal Growth Factor Scattering Microfilament Proteins Biological Sciences Extracellular Matrix Nanostructures Protein Structure Tertiary Kinetics Microscopy Electron Crystallography Models Chemical Membrane protein Biophysics Heparitin Sulfate Microfibril Fibrillin |
| Zdroj: | Proceedings of the National Academy of Sciences. 103:11922-11927 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Fibrillin-1 is a 330-kDa multidomain extracellular matrix protein that polymerizes to form 57-nm periodic microfibrils, which are essential for all tissue elasticity. Fibrillin-1 is a member of the calcium-binding EGF repeat family and has served as a prototype for structural analyses. Nevertheless, both the detailed structure of fibrillin-1 and its organization within microfibrils are poorly understood because of the complexity of the molecule and the resistance of EGF arrays to crystallization. Here, we have used small-angle x-ray scattering and light scattering to analyze the solution structure of human fibrillin-1 and to produce ab initio structures of overlapping fragments covering 90% of the molecule. Rather than exhibiting a uniform rod shape as current models predict, the scattering data revealed a nonlinear conformation of calcium-binding EGF arrays in solution. This finding has major implications for the structures of the many other EGF-containing extracellular matrix and membrane proteins. The scattering data also highlighted a very compact, globular region of the fibrillin-1 molecule, which contains the integrin and heparan sulfate-binding sites. This finding was confirmed by calculating a 3D reconstruction of this region using electron microscopy and single-particle image analysis. Together, these data have enabled the generation of an improved model for microfibril organization and a previously undescribed mechanism for microfibril extensibility. |
| Databáze: | OpenAIRE |
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