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Collagens are They are essential structural components of all connective tissues, such as Gelatin is solubilized collagen.

29 types of collagens have been found in humans. The major ones are:

The other 25 types are probably equally important but they are much less abundant.

Primary Structure of Collagens

The basic unit of collagens is a polypeptide consisting of the repeating sequence

(glycine (Gly) - X - Y)n

where X is often proline (Pro) and Y is often hydroxyproline (proline to which an -OH group is added after synthesis of the polypeptide).

Secondary and Tertiary Structure

The resulting molecule twists into an elongated, left-handed helix (NOT an alpha helix). When synthesized, the N- terminal and C- terminal of the polypeptide have globular domains, which keep the molecule soluble.

As they pass through the endoplasmic reticulum (ER) and Golgi apparatus,

In some collagens (e.g., Type II), the three molecules are identical (the product of a single gene). In other collagens (e.g., Type I), two polypeptides of one kind (gene product) assemble with a second, quite similar, polypeptide, that is the product of a second gene.

When the triple helix is secreted from the cell (usually by a fibroblast), the globular ends are cleaved off. The resulting linear, insoluble molecules assemble into collagen fibers. They assemble in a staggered pattern that gives rise to the striations seen in this electron micrograph (courtesy of Dr. Jerome Gross). (Type IV collagens are an exception; they form a meshwork rather than striated fibers.)

Inherited Diseases Caused by Mutant Collagen Genes

Brittle-bone disease ("osteogenesis imperfecta")

Caused by a mutation in one or the other of the two genes whose products are used to make Type I collagen. Like all the inherited collagen diseases, this one is inherited as a dominant trait. The reason: even though one collagen allele is normal, the assembly of the normal gene product with the mutant product produces defective collagen fibers.

Bone marrow stem cells from patients with this disease have had their mutant gene knocked out by gene targeting [Link] and gained the ability to make good collagen and bone (when the cells were placed in immunodeficient mice). So this disease now seems to be a promising candidate for gene therapy.

Some forms of dwarfism

Caused by mutations in a Type II collagen gene.

Rubber-man syndrome

Caused by a mutations in a Type I collagen gene. The subject has hyperextensible joints, tendons, and skin. (This inherited disorder represents one type of Ehlers-Danlos syndrome.)

Another type of Ehlers-Danlos syndrome

Is caused by mutations in the gene for Type III collagen. Patients are at risk of rupture of major arteries or the intestine.

Alport's syndrome

Most cases involve mutations in the gene on the X chromosome for one of the chains of Type IV collagen. So it shows the typical pattern of X-linked inheritance.

Other cases are caused by two mutant autosomal genes for another of the Type IV collagen chains.

Patients usually have damage to their glomeruli, leading to blood in their urine and, often, become deaf as well.

Herniated discs between the vertebrae?

A study in Finland has found that some families that share a tendency to develop herniated discs (leading to sciatica) have an inherited point mutation in the gene (COL9A2) encoding one of the alpha chains in collagen IX. This collagen is one component of the extracellular matrix in the padding (discs) between our vertebrae.

Other Collagen Diseases


Caused by a deficiency of vitamin C. The sufferer is unable to add hydroxyl (-OH) groups to proline to convert it into hydroxyproline.

Goodpasture's Syndrome

Some people develop antibodies against an epitope on their Type IV collagen molecules. These

So Goodpasture's syndrome is an example of an autoimmune disorder.

The basal lamina of the lung epithelia and the glomeruli of the kidney are especially likely to be affected. In this photo (courtesy of Dr. Frank J. Dixon), a fluorescent antibody against human IgG shows the autoantibodies coating the basement membranes of the glomeruli in a patient with Goodpasture's syndrome.

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13 January 2011