Collagen is the major constituent of bone matrix. It is a crystalline fibroprotein fibril with characteristic x-ray diffraction and electron microscopic pattern, having a periodicity of about 6400 nm, although its length, diameter and density vary with age.
In very old bone its diameter may be over 1000 nm.
Collagen is also the major extracellular protein of the body and comprises some 30 percent today body protein.Important advances have been made in the elucidation of the structure of the precursors, or procollagens, of tissue collagen, in the discovery of new types of collagen and in the mechanisms of collagen degradation.
However, though much is known of the intermediary metabolism of collagen, little is known of what controls the deposition and orientation of collagen fibres in the tissues or the quantity of collagen that is formed.
Collagen Structure
A collagen molecule is composed of three, distinct, polypeptide chains wound round each other to form a triple helix. The collagen helix will form spontaneously from individual polypeptide chains, or alpha (?) chains, when they are incubated under the appropriate conditions of salt concentration, pH and temperature.
This triple helical structure results in a long rigid molecule some 300 nm long and 1 nm wide. The triple helix of human collagen can be dissociated at temperatures above 40 degree C.
The amino acid composition of the alfa chains is unusual. One-third of the total number of amino acid residues is glycine, and one-fifth proline and its derivative, hydroxyproline. Hydroxyproline is almost solely confined to collagen. In addition, collagen contains hydroxylysine and several oxidized derivatives of lysine (and hydroxylysiine); these derivatives are involved in the chemical links which joint together the individual collagen molecules within a collagen fibre.
Amino acid sequence analysis has shown that the alfa chains have the general composition (glycine X-Y) with Y often hydroxyproline. It is this repeating sequence which allows the three alfa chains to form the triple helix of the collagen molecule.
The collagen molecule is first synthesized as a precursor, procollagen, which consists of three pro-alfa chains. Each pro-alfa chain contains several distinct regions. The N-terminal region has the structure of a typical globular protein which is maintained by internal –S-S- links. Next there is a short region with composition (Gly-X-Y)n which can interact with two other pro-alfa chains to form the typical collagen triple helix.
This is followed by a short non-collagenous sequence and then the main length of repeating (Gly-X-Y)n triplets. The carboxyl terminal region which joins this collagenous sequence is joined by external –S-S- links to the two other pro-alfa chains which ofrm a procollagen molecule.
During biosynthesis the long terminal regions are cleaved by specific proteases to form a collagen molecule consisting of the central (Gly-X-Y)n region and flanked by two non-collagenous sequences, or telopeptides, of some 10-30 amino acid residues.
The assembly of the molecules appears to be determined chiefly by distribution of charged amino acids along the sequence of the three alfa chains, but can be influenced by various substances, as for example, the proteoglycans with which collagen is associated in vivo. The collagen fibrils show an asymmetric cross-striation pattern with a periodicity of 68 nm with each molecule being 4.4 times this repeat period.
The fibers themselves may be formed from bundles of microfibrils, each of which consists of five collagen molecules lying side by side but displaced by the repeat pattern and rolled together to form a long fibril, which in cross-section containts different parts of five collagen molecules (or four molecules and a gap) at any specific level. The physiological control of microfibril formation or of the lateral aggregation of these microfibrils remains unknown.
In vivo and in vitro chemical cross-links form between the individual collagen molecules that together make a collagen fibre. These links originate helical regions of the molecule. It is the formation of these corss-links that renders a collagen fibre resistant to tensile forces In practice, then, a solution of collagen will contain not only individual collagen molecules but also polymers of cross-linked moleculaes.
As a result, if the solution is heated to denature the collagen triple helix, not only individual alfa chains are released but also units of twice and thrice with the size of alfa chains consisting of two, three alfa chains joined together by cross-links. These polypeptides are known as beta, gama units and can be distinguished from alfa chains on gel chromatography or electrophoresis.
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