Type I collagen is the most abundant

collagen Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

of the human body, consisting of around 90% of the body's total collagen in vertebrates. Due to this, it is also the most abundant protein type found in all vertebrates. Type I forms large,

eosinophilic Eosinophilic (Greek suffix '' -phil'', meaning ''eosin-loving'') describes the staining of tissues, cells, or organelles after they have been washed with eosin, a dye commonly used in histological staining. Eosin is an acidic dye for stainin ...

fibers known as collagen fibers, which make up most of the rope-like dense connective tissue in the body. Collagen I itself is created by the combination of both a proalpha1 and a proalpha2 chain created by the COL1alpha1 and COL1alpha2 genes respectively. The Col I gene itself takes up a triple-helical conformation due to its

Glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

-X-Y structure, x and y being any type of amino acid. Collagen can also be found in two different isoforms, either as a homotrimer or a heterotrimer, both of which can be found during different periods of development. Heterotrimers, in particular, play an important role in wound healing, and are the dominant isoform found in the body. Type I collagen can be found in a myriad of different places in the body, mainly forming the matrix of connective tissues. It is present in scar tissue as well as

tendons A tendon or sinew is a tough band of dense fibrous connective tissue that connects muscle to bone. It sends the mechanical forces of muscle contraction to the skeletal system, while withstanding tension. Tendons, like ligaments, are made of ...

ligaments A ligament is a type of fibrous connective tissue in the body that connects bones to other bones. It also connects flight feathers to bones, in dinosaurs and birds. All 30,000 species of amniotes (land animals with internal bones) have ligam ...

, the

endomysium The endomysium, meaning ''within the muscle'', is a wispy layer of areolar connective tissue that ensheaths each individual muscle fiber, or muscle cell. It also contains capillaries and nerves. It overlies the muscle fiber's cell membrane: th ...

myofibrils A myofibril (also known as a muscle fibril or sarcostyle) is a basic rod-like organelle of a muscle cell. Skeletal muscles are composed of long, tubular cells known as muscle fibers, and these cells contain many chains of myofibrils. Each myofibr ...

, the organic part of

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

, the

dermis The dermis or corium is a layer of skin between the epidermis (skin), epidermis (with which it makes up the cutis (anatomy), cutis) and subcutaneous tissues, that primarily consists of dense irregular connective tissue and cushions the body from s ...

, the

dentin Dentin ( ) (American English) or dentine ( or ) (British English) () is a calcified tissue (biology), tissue of the body and, along with tooth enamel, enamel, cementum, and pulp (tooth), pulp, is one of the four major components of teeth. It i ...

, and organ capsules.

Formation

The creation process of type I Collagen begins with the production and the combination of two separate subunits, called the pro-alpha1(I) and pro-alpha2(I) chains. These pro-alpha chains are encoded by the COL1A1 and COL1A2 genes respectively and when combined produce type I pro-collagen. This transcriptional process takes place within the cell's

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

and must undergo post-translational modifications in order to make the final type I collagen product. The procollagen complex is then modified by different enzyme proteinases which cleave N and C terminal pro-peptides that are present on either side of the molecule. This process occurs outside of the cellular membrane at which post processing, the molecules cross link and form a final type I collagen product.

Structure

Type I collagen has a triple-helical form which is caused by its amino acid composition. Its specific domain follows an order of G-X-Y In which the X and Y slots are occupied by any amino acid other than glycine however these slots are typically occupied by both

hydroxyproline (2''S'',4''R'')-4-Hydroxyproline, or L-hydroxyproline ( C5 H9 O3 N), is an amino acid, abbreviated as Hyp or O, ''e.g.'', in Protein Data Bank. Structure and discovery In 1902, Hermann Emil Fischer isolated hydroxyproline from hydrolyzed gela ...

and

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

, not in any particular order. This specific conformation will end up being repeated and packed into a hexagonal structure in order to form collagen fibrils. The molecular mass of type I collagen is 300,000 g/mol and assembles in one of two higher order molecular assemblies. It forms a large solid structure formed by strict and non-flexible protein interactions. This large multi-protein structure is crucially held together by mainly hydrogen bonds and the fibrils conform to a typical diameter size between 25 - 400

nanometers 330px, Different lengths as in respect to the molecular scale. The nanometre (international spelling as used by the International Bureau of Weights and Measures; SI symbol: nm), or nanometer (American and British English spelling differences#-r ...

in this fibril conformation.

Implications in Disease

Mutations in genes encoding collagen type 1 are known to cause a myriad of different conditions including: Cardiac Valvular type Ehlers-Danlos Syndrome: This type of Ehlers-Danlos is caused by mutations within the COL1alpha2 gene, which is responsible for encoding the collagen pro-alpha2 chain. Vascular type Ehlers-Danlos Syndrome: Some patients with Vascular type Ehlers-Danlos, which is caused by mutations in COL3alpha1, are known to also have mutations in the COL1alpha1 gene. However the exact associations remain unknown. Athrochalasia type Ehlers-Danlos Syndrome: This type of Ehlers-Danlos is caused by the mutation of the COL1alpha1 and COL1alpha2 genes, which are responsible for encoding the proalpha1 and proalpha2 chains respectively.

Osteogenesis Imperfecta Osteogenesis imperfecta (; OI), colloquially known as brittle bone disease, is a group of genetic disorders that all result in bones that bone fracture, break easily. The range of symptoms—on the skeleton as well as on the body's other Or ...

(types 1–4): Mutations in COL1alpha 1 and/or COL1alpha2 are known to cause several different types of Osteogenesis Imperfecta with the severity of said diseases being related to the type and frequency of the mutations occurring. For further information on COL1's effect in this disease, see Collagen, type 1, alpha 1. Caffey Disease: This condition is caused by a mutation in the COL1alpha gene that replaces arginine with cysteine at the 836 protein site. This particular mutation causes the fibrils of type I to vary greatly in size and shape.

Clinical significance

See Collagen, type I, alpha 1#Clinical significance Markers used to measure bone loss are not easily testable. Degradation of type I collagen releases metabolites that can be used to monitor resorption.

References

* {{Fibrous proteins Collagens

Formation

Structure

Implications in Disease

Clinical significance

See also

References