Journal article
Nanostructure of fibrillin-1 reveals compact conformation of EGF arrays and mechanism for extensibility
Proceedings of the National Academy of Sciences of the United States of America, Vol.103(32), pp.11922-11927
2006
Abstract
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. © 2006 by The National Academy of Sciences of the USA.
Details
- Title
- Nanostructure of fibrillin-1 reveals compact conformation of EGF arrays and mechanism for extensibility
- Authors
- Clair Baldock (Author) - University of Manchester, United KingdomV Siegler (Author) - University of Cardiff, United KingdomD V Bax (Author) - University of Manchester, United KingdomS A Cain (Author) - University of Manchester, United KingdomK T Mellody (Author) - University of Manchester, United KingdomA Marson (Author) - University of Manchester, United KingdomJ L Haston (Author) - University of Cardiff, United KingdomR Berry (Author) - University of Manchester, United KingdomM C Wang (Author) - University of Manchester, United KingdomJ G Grossmann (Author) - Daresbury Laboratory, United KingdomM Roessle (Author) - European Synchrotron Radiation Facility, FranceC M Kielty (Author) - University of Manchester, United KingdomTim J Wess (Author) - University of Cardiff, United Kingdom
- Publication details
- Proceedings of the National Academy of Sciences of the United States of America, Vol.103(32), pp.11922-11927
- Publisher
- National Academy of Sciences
- Date published
- 2006
- DOI
- 10.1073/pnas.0601609103
- ISSN
- 0027-8424; 0027-8424
- Organisation Unit
- Office of the Deputy Vice-Chancellor (Academic); University of the Sunshine Coast, Queensland
- Language
- English
- Record Identifier
- 99451406802621
- Output Type
- Journal article
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