Fibrillin

Last updated
fibrillin 1
2W86 (Fibrillin).png
Crystallographic structure of the cbEGF9-hybrid2-cbEGF10 region of human fibrillin 1. [1]
Identifiers
Symbol FBN1
Alt. symbolsFBN, MFS1, WMS
NCBI gene 2200
HGNC 3603
OMIM 134797
PDB 2W86
RefSeq NM_000138
UniProt P35555
Other data
Locus Chr. 15 q21.1
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Structures Swiss-model
Domains InterPro
fibrillin 2
Identifiers
SymbolFBN2
Alt. symbolsCCA
NCBI gene 2201
HGNC 3604
OMIM 121050
RefSeq NM_001999
UniProt P35556
Other data
Locus Chr. 5 q23-q31
Search for
Structures Swiss-model
Domains InterPro
fibrillin 3
Identifiers
SymbolFBN3
NCBI gene 84467
HGNC 18794
OMIM 608529
RefSeq NM_032447
UniProt Q75N90
Other data
Locus Chr. 19 p13
Search for
Structures Swiss-model
Domains InterPro

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]

Contents

Clinical aspects

Marfan syndrome is a genetic disorder of the connective tissue caused by defected FBN1 gene. Mutations in FBN1 and FBN2 are also sometimes 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 Beals 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   2724076 . PMID   19446531.
  2. ↑ Kielty CM, Baldock C, Lee D, Rock MJ, Ashworth JL, Shuttleworth CA (February 2002). "Fibrillin: from microfibril assembly to biomechanical function". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 357 (1418): 207–17. doi:10.1098/rstb.2001.1029. PMC   1692929 . PMID   11911778.
  3. ↑ Singh (2006). Textbook of human histology. Jaypee Brothers Publishers. pp. 64–. ISBN   978-81-8061-809-3 . Retrieved 9 December 2010.[ permanent dead link ]
  4. ↑ Buchan JG, Alvarado DM, Haller GE, Cruchaga C, Harms MB, Zhang T, Willing MC, Grange DK, Braverman AC, Miller NH, Morcuende JA, Tang NL, Lam TP, Ng BK, Cheng JC, Dobbs MB, Gurnett CA (October 2014). "Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis". Human Molecular Genetics. 23 (19): 5271–82. doi:10.1093/hmg/ddu224. PMC   4159151 . PMID   24833718.
  5. ↑ Sakai LY, Keene DR, Engvall E (December 1986). "Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils". The Journal of Cell Biology. 103 (6 Pt 1): 2499–509. doi:10.1083/jcb.103.6.2499. PMC   2114568 . PMID   3536967.
  6. ↑ Dietz HC (August 2010). "New therapeutic approaches to mendelian disorders". The New England Journal of Medicine. 363 (9): 852–63. doi: 10.1056/NEJMra0907180 . PMID   20818846.
  7. 1 2 von Kodolitsch Y, De Backer J, Schüler H, Bannas P, Behzadi C, Bernhardt AM, Hillebrand M, Fuisting B, Sheikhzadeh S, Rybczynski M, Kölbel T, Püschel K, Blankenberg S, Robinson PN (2015). "Perspectives on the revised Ghent criteria for the diagnosis of Marfan syndrome". The Application of Clinical Genetics. 8: 137–55. doi: 10.2147/TACG.S60472 . PMC   4476478 . PMID   26124674.
  8. ↑ Zhang H, Apfelroth SD, Hu W, Davis EC, Sanguineti C, Bonadio J, Mecham RP, Ramirez F (March 1994). "Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices". The Journal of Cell Biology. 124 (5): 855–63. doi:10.1083/jcb.124.5.855. PMC   2119952 . 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". Developmental Dynamics. 237 (10): 2844–61. doi:10.1002/dvdy.21705. PMC   3081706 . PMID   18816837.
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