Fibrillin

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.

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, and mutations in the FBN1 gene cause Marfan syndrome.

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

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. 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 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. 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.

References

References

1. (May 2009). "Structure and interdomain interactions of a hybrid domain: a disulphide-rich module of the fibrillin/LTBP superfamily of matrix proteins". Structure.
2. (February 2002). "Fibrillin: from microfibril assembly to biomechanical function". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences.
3. Singh. (March 2024). "Textbook of human histology". Jaypee Brothers Publishers.
4. (October 2014). "Rare variants in FBN1 and FBN2 are associated with severe adolescent idiopathic scoliosis". Human Molecular Genetics.
5. (December 1986). "Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils". The Journal of Cell Biology.
6. (August 2010). "New therapeutic approaches to mendelian disorders". The New England Journal of Medicine.
7. (2015). "Perspectives on the revised Ghent criteria for the diagnosis of Marfan syndrome". The Application of Clinical Genetics.
8. (March 1994). "Structure and expression of fibrillin-2, a novel microfibrillar component preferentially located in elastic matrices". The Journal of Cell Biology.
9. (March 2004). "Differential expression of fibrillin-3 adds to microfibril variety in human and avian, but not rodent, connective tissues". Genomics.
10. (October 2008). "Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis". Developmental Dynamics.