|Alt. symbols||FBN, MFS1, WMS|
|Locus||Chr. 15 q21.1|
|Locus||Chr. 5 q23-q31|
|Locus||Chr. 19 p13|
Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue. Fibrillin is secreted into the extracellular matrix by fibroblasts and becomes incorporated into the insoluble microfibrils, which appear to provide a scaffold for deposition of elastin.
Fibrillin-1 is a major component of the microfibrils that form a sheath surrounding the amorphous elastin. It is believed that the microfibrils are composed of end-to-end polymers of fibrillin. To date, 3 forms of fibrillin have been described. The fibrillin-1 protein was isolated by Engvall in 1986, and mutations in the FBN1 gene cause Marfan syndrome.
This protein is found in humans, and its genes are found on chromosome 15. At present more than 600 different mutations have been described.
There is no complete, high-resolution structure of fibrillin-1. Instead, short fragments have been produced recombinantly and their structures solved by X-ray crystallography or using NMR spectroscopy. A recent example is the structure of the fibrillin-1 hybrid2 domain, in context of its flanking calcium binding epidermal growth factor domains, which was determined using X-ray crystallography to a resolution of 1.8 Å. The microfibrils that are made up of fibrillin protein are responsible for different cell-matrix interactions in the human body.
More recently, fibrillin-3 was described and is believed to be located mainly in the brain. Along with the brain, fibrillin-3 has been localized in the gonads and ovaries of field mice.
Fibrillin-4 was first discovered in zebrafish, and has a sequence similar to fibrillin-2.
- PDB 2W86; Jensen SA, Iqbal S, Lowe ED, Redfield C, Handford PA (May 2009). "Structure and interdomain interactions of a hybrid domain: a disulphide-rich module of the fibrillin/LTBP superfamily of matrix proteins". Structure 17 (5): 759–68. PMC 2724076. PMID 19446531. doi:10.1016/j.str.2009.03.014.
- Kielty CM, Baldock C, Lee D, Rock MJ, Ashworth JL, Shuttleworth CA (February 2002). "Fibrillin: from microfibril assembly to biomechanical function". Philos. Trans. R. Soc. Lond., B, Biol. Sci. 357 (1418): 207–17. PMC 1692929. PMID 11911778. doi:10.1098/rstb.2001.1029.
- Singh (2006). Textbook of human histology. Jaypee Brothers Publishers. pp. 64–. ISBN 978-81-8061-809-3. Retrieved 9 December 2010.
- Buchan, J. G.; Alvarado, D. M.; Haller, G. E.; Cruchaga, C; Harms, M. B.; Zhang, T; Willing, M. C.; Grange, D. K.; Braverman, A. C.; Miller, N. H.; Morcuende, J. A.; Tang, N. L.; Lam, T. P.; Ng, B. K.; Cheng, J. C.; Dobbs, M. B.; Gurnett, C. A. (2014). "Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis". Human Molecular Genetics 23: 5271–5282. PMID 24833718. doi:10.1093/hmg/ddu224.
- Sakai LY, Keene DR, Engvall E (December 1986). "Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils". J. Cell Biol. 103 (6 Pt 1): 2499–509. PMC 2114568. PMID 3536967. doi:10.1083/jcb.103.6.2499.
- Dietz HC; Guttmacher, Alan E.; Dietz, Harry C. (August 2010). "New therapeutic approaches to mendelian disorders". N. Engl. J. Med. 363 (9): 852–63. PMID 20818846. doi:10.1056/NEJMra0907180.
- Zhang H, Apfelroth SD, Hu W et al. (1994). "Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices". J. Cell Biol. 124 (5): 855–63. PMC 2119952. PMID 8120105. doi:10.1083/jcb.124.5.855.
- Corson GM, Charbonneau NL, Keene DR, Sakai LY (March 2004). "Differential expression of fibrillin-3 adds to microfibril variety in human and avian, but not rodent, connective tissues". Genomics 83 (3): 461–72. PMID 14962672. doi:10.1016/j.ygeno.2003.08.023.
- Gansner JM, Madsen EC, Mecham RP, Gitlin JD (October 2008). "Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis". Dev. Dyn. 237 (10): 2844–61. PMC 3081706. PMID 18816837. doi:10.1002/dvdy.21705.