Fibrillin is a
glycoprotein, which is essential for the formation of
elastic fibers found in
connective tissue.
Fibrillin is secreted into the
extracellular matrix
In biology, the extracellular matrix (ECM), also called intercellular matrix, is a three-dimensional network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide s ...
by
fibroblasts
A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...
and becomes incorporated into the insoluble microfibrils, which appear to provide a scaffold
for deposition of
elastin.
Clinical aspects
Marfan syndrome is a genetic disorder of the connective tissue caused by defected
FBN1
Fibrillin-1 is a protein that in humans is encoded by the ''FBN1'' gene, located on chromosome 15. It is a large, extracellular matrix glycoprotein that serves as a structural component of 10-12 nm calcium-binding microfibrils. These microfib ...
gene. Mutations in
FBN1
Fibrillin-1 is a protein that in humans is encoded by the ''FBN1'' gene, located on chromosome 15. It is a large, extracellular matrix glycoprotein that serves as a structural component of 10-12 nm calcium-binding microfibrils. These microfib ...
and
FBN2
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, whi ...
are also sometimes associated with
adolescent idiopathic scoliosis.
Types
Fibrillin-1
Fibrillin-1 is a major component of the
microfibril A microfibril is a very fine fibril, or fiber-like strand, consisting of glycoproteins and cellulose. It is usually, but not always, used as a general term in describing the structure of protein fiber, e.g. hair and sperm tail. Its most frequently ...
s that form a sheath surrounding the amorphous
elastin. It is believed that the
microfibril A microfibril is a very fine fibril, or fiber-like strand, consisting of glycoproteins and cellulose. It is usually, but not always, used as a general term in describing the structure of protein fiber, e.g. hair and sperm tail. Its most frequently ...
s are composed of end-to-end
polymer
A polymer (; Greek '' poly-'', "many" + ''-mer'', "part")
is a substance or material consisting of very large molecules called macromolecules, composed of many repeating subunits. Due to their broad spectrum of properties, both synthetic a ...
s 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
Elastic fibers (or yellow fibers) are an essential component of the extracellular matrix composed of bundles of proteins ( elastin) which are produced by a number of different cell types including fibroblasts, endothelial, smooth muscle, and ai ...
. Mutations in the fibrillin-2 gene have been linked to
Beals syndrome
Congenital contractural arachnodactyly (CCA), also known as Beals-Hecht syndrome, is a rare autosomal dominant congenital connective tissue disorder. As with Marfan syndrome, people with CCA typically have an arm span that is greater than their hei ...
.
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
External links
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{{Connective tissue
Structural proteins