fibrillin 1
Crystallographic structure of the cbEGF9-hybrid2-cbEGF10 region of human fibrillin 1.[1]
Identifiers
Symbol	FBN1
Alt. symbols	FBN, 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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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 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]