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The below mentioned article provides a short note on Collagen:- 1. Introduction to Collagen 2. Synthesis of Collagen 3. Inherited Defects.
Introduction to Collagen:
1. Collagen is the major macromolecule of connective tissues and it is the most common protein in the animal kingdom.
2. In mammalian tissues, there are five distinct types of collagen and they exist as a family of molecules sharing many properties.
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3. The most important property of collagen molecules is their triple helix, a coiled coil of three polypeptide subunits. Each polypeptide subunit is twisted into a left- handed helix of 3 residues per turn. Three of these left-handed helices are then wound to a right-handed super helix to form a stiff rod like molecule 1.4 nm in diameter and about 300 nm long.
These triple helical molecules are associated into fibrils. There is a gap between the end of one triple helix and the beginning of the next where there is the deposition of hydroxyapatite crystals in bone formation.
4. The collagen fibres range from 10 to 100 nm in diameter and are visible by microscopy as banded structures in the extracellular matrix of connective tissues.
5. Glycine is the only amino acid to exist in the limited space available down the central core of the triple helical molecule.
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6. In mammalian collagen, about 100 of the X positions are proline and 100 of the y positions are 4-hydroxyproline. They also contain 3-hydroxyproline in some X positions and 5-hydroxylysine in y positions.
Synthesis of Collagen:
1. Collagen is an extracellular protein but it is synthesized as an intracellular precursor molecule before becoming a mature collagen fibril.
2. Pre-pro-collagen, a precursor of collagen, contains a leader or signal sequence of about 100 amino acids at its amino-terminus. This pre-pro-collagen is generated by ribosomes attached to the endoplasmic reticulum.
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3. When the signal sequence penetrates into the vesicular space of the endoplasmic reticulum, the leader sequence is cleaved off and the amino-terminal end of pro-collagen continues to protrude into the endoplasmic reticular space.
At this site, prolyl 4-hydroxylase and lysyl hydroxylase acts on proline or lysine residues respectively in the y position of the (Gly-X- γ)n Peptide. A prolyl 3-hydroxylase in the X position immediately preceeding a 4- hydroxyproline in the γ position.
4. The pro-collagen molecule contains at its amino-terminus a 20,000-MW peptide and at its carboxyl-terminus a 30-35 thousand- MW peptide. Neither of these is present in mature collagen.
5. After formation of triple helix, further hydroxylation of prolyl and lysyl residues cannot take place.
6. After this intercellular processing, the glycosylated pro-collagen molecule reaches the outside of the cell by way of the Golgi complex. Extracellular pro-collagen amino-protease and pro-collagen mrhoxyprotcase remove the amino-terminal and carboxyl-terminal pro-peptides, respectively.
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The newly formed collagen molecules have about 1,000 amino acids and spontaneously assemble into collagen fibrils that are indistinguishable from the mature fibrils found in tissues. These fibrils do not have the tensile strength of mature collagen fibrils until they are cross-linked by a series of corn- lent bonds.
Inherited Defects of Collagen:
Type VI Ehlers-Danlos Syndrome:
1. This is an inherited deficiency of lysyl hydroxylase.
2. This disease is characterized by frequent abnormalities of the eye, severe scoliosis (abnormal vertebral column curvature) and hyper-extensibility of the skin and joints.
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Type V Ehlers-Danlols Syndrome:
1. This is due to the deficiency of lysyl oxidase activity. The absence of this enzyme prevents normal cross-linking of collagen. Lysyl oxidase is a copper-requiring enzymes.
2. There is severe arteriovascular and skeletal change.
Type VII Ehlers-Danlos Syndrome:
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1. This is caused due to the non-serving of procollagen as a substrate for the procollagen aminoprotease.
2. The patients have hip dislocations, increased skin elasticity, and short stature.
