Fibrillin

fibrillin 1

Crystallographic structure of the cbEGF9-hybrid2-cbEGF10 region of human fibrillin 1.[1]
Identifiers
Symbol FBN1
Alt. symbols FBN, MFS1, WMS
Entrez 2200
HUGO 3603
OMIM 134797
PDB 2W86
RefSeq NM_000138
UniProt P35555
Other data
Locus Chr. 15 q21.1
fibrillin 2
Identifiers
Symbol FBN2
Alt. symbols CCA
Entrez 2201
HUGO 3604
OMIM 121050
RefSeq NM_001999
UniProt P35556
Other data
Locus Chr. 5 q23-q31
fibrillin 3
Identifiers
Symbol FBN3
Entrez 84467
HUGO 18794
OMIM 608529
RefSeq NM_032447
UniProt Q75N90
Other data
Locus Chr. 19 p13

Fibrillin is a glycoprotein, which is essential for the formation of elastic fibers found in connective tissue.[2] 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.[3]

Clinical aspect

Mutations in FBN1 and FBN2 are associated with adolescent idiopathic scoliosis .[4]

Types

Fibrillin-1

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,[5] and mutations in the FBN1 gene cause Marfan syndrome.[6][7]

This protein is found in humans, and its gene is found on chromosome 15. At present more than 1500 different mutations have been described.[1][7]

Structure

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.[1] The microfibrils that are made up of fibrillin protein are responsible for different cell-matrix interactions in the human body.

Fibrillin-2

Fibrillin-2 was isolated in 1994 by Zhang[8] and is thought to play a role in early elastogenesis. Mutations in the fibrillin-2 gene have been linked to Beal's Syndrome.

Fibrillin-3

More recently, fibrillin-3 was described and is believed to be located mainly in the brain.[9] Along with the brain, fibrillin-3 has been localized in the gonads and ovaries of field mice.

Fibrillin-4

Fibrillin-4 was first discovered in zebrafish, and has a sequence similar to fibrillin-2.[10]

References

  1. 1 2 3 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. doi:10.1016/j.str.2009.03.014. PMC 2724076Freely accessible. PMID 19446531.
  2. ↑ 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. doi:10.1098/rstb.2001.1029. PMC 1692929Freely accessible. PMID 11911778.
  3. ↑ Singh (2006). Textbook of human histology. Jaypee Brothers Publishers. pp. 64–. ISBN 978-81-8061-809-3. Retrieved 9 December 2010.
  4. ↑ 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. doi:10.1093/hmg/ddu224. PMID 24833718.
  5. ↑ 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. doi:10.1083/jcb.103.6.2499. PMC 2114568Freely accessible. PMID 3536967.
  6. ↑ Dietz HC; Guttmacher, Alan E.; Dietz, Harry C. (August 2010). "New therapeutic approaches to mendelian disorders". N. Engl. J. Med. 363 (9): 852–63. doi:10.1056/NEJMra0907180. PMID 20818846.
  7. 1 2 von Kodolitsch Y (2015). "Perspectives on the revised Ghent criteria for the diagnosis of Marfan syndrome". Application of Clinical Genetics. 8: 137–155. doi:10.2147/TACG.S60472. PMC 4476478Freely accessible. PMID 26124674.
  8. ↑ 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. doi:10.1083/jcb.124.5.855. PMC 2119952Freely accessible. PMID 8120105.
  9. ↑ 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. doi:10.1016/j.ygeno.2003.08.023. PMID 14962672.
  10. ↑ 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. doi:10.1002/dvdy.21705. PMC 3081706Freely accessible. PMID 18816837.

External links

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