e) β Myosin heavy chain
The right answer is – c) Collagen.
Osteogenesis imperfecta (OI) is predominantly characterized by a generalized decrease in bone mass (osteopenia) and by brittle bones. The disorder is frequently associated with blue sclerae, dental abnormalities (dentinogenesis imperfecta), progressive hearing loss, and a positive family history.
The disorder is caused by mutations in the genes that code for type I procollagen (ie, COL1A1 and COL1A2).
General discussion of collagen
Collagen is the most abundant protein of the human body accounting to around 25-30% of the total protein content. It is the major component of most connective tissues. It is also the main fibrous component of skin, bone, tendon, cartilage, and teeth. Collagen is a Greek word which means “Glue”, it is so named since it holds the cells together in the tissues.
Types of collagen
Twenty-eight different collagens made up of over 30 distinct polypeptide chains (each encoded by a separate gene) have been identified in human tissues. Many are minor constituents that probably have highly specialized functions. They may play important roles in determining the physical properties of specific tissues.
In addition, a number of proteins (eg, the C1q component of the complement system, pulmonary surfactant proteins SP-A and SP-D) that are not classified as collagens have collagen-like domains in their structures; these proteins are sometimes referred to as “noncollagen collagens.”
The major types are as follows-
1) Type I collagen is found throughout the body except in cartilaginous tissues. It is found in skin, tendon, vascular, ligature, organs and is the main component of bone. It is also synthesized in response to injury and in the fibrous nodules in fibrous diseases. Over 90% of the collagen in the body is type I.It is synthesized from the genes COL1A1, COL1A2. The mutations of these genes are responsible for ‘Osteogenesis Imperfecta“.
2) Type II collagen is the main component of cartilage. It is also found in developing cornea and vitreous humor. These are formed from two or more collagens or co-polymers rather than a single type of collagen.It is synthesized from the genes COL2A1.
3) Type III collagen is found in the extensible connective tissues such as skin, lung, and the vascular system such as walls of arteries and other hollow organs and usually occurs in the same fibril with type I collagen. The gene responsible for this is COL3A1.
4) Type IV collagen forms the bases of cell basement membrane. The genes for this type are COL4A1–COL4A6
5) Type V collagen is a minor components of tissue and occurs as fibrils with type I and type II collagen respectively. Type V forms cell surfaces, hair and placenta. It is synthesized from COL5A1–COL5A3.
6) Type VI Collagen is present in most connective tissues and is derived from the genes COL6A1–COL6A3.
Structure of collagen
All collagen types have a triple helical structure. In some collagens, the entire molecule is triple helical, whereas in others the triple helix may involve only a fraction of the structure.
Mature collagen type I, containing approximately 1000 amino acids, belongs to the former type; in it, each polypeptide subunit or alpha chain is twisted into a left-handed helix of three residues per turn. Three of these alpha chains are then wound into a right-handed superhelix, forming a rod-like molecule 1.4 nm in diameter and about 300 nm long (Figure-1).
Figure-1- Each individual polypeptide chain is twisted into a left-handed helix of three residues (Gly-X-Y) per turn, and all of these chains are then wound into a right-handed superhelix.
Amino acid composition of collagen
A striking characteristic of collagen is the occurrence of glycine residues at every third position of the triple helical portion of the alpha chain. This is necessary because glycine is the only amino acid small enough to be accommodated in the limited space available down the central core of the triple helix. This repeating structure, represented as (Gly-X-Y)n, is an absolute requirement for the formation of the triple helix. While X and Y can be any other amino acids, about 100 of the X positions are proline and about 100 of the Y positions are hydroxy proline. Proline and hydroxy proline confer rigidity on the collagen molecule.
Hydroxylation of Proline and Lysine
Hydroxy proline is formed by the posttranslational hydroxylation of peptide-bound proline residues catalyzed by the enzyme prolyl hydroxylase, whose cofactors are ascorbic acid (vitamin C) and α-ketoglutarate. Vitamin C deficiency causes impaired hydroxylation , and defective collagen synthesis and hence is responsible for the disease scurvy. The hydroxylation is site specific, hence proline is hydroxylated to 4-hydroxy proline or 3-hydroxy proline depending upon its location relative to glycine.
Lysines in the Y position may also be posttranslationally modified to hydroxylysine through the action of lysyl hydroxylase, an enzyme with similar cofactors. Lysine is hydroxylated at position -5. The hydroxylated amino acids are of special functional significance.
Glycosylation of amino acyl residues in collagen
Some of these hydroxylysines may be further modified by the addition of galactose or galactosyl-glucose through an O-glycosidic linkage, a glycosylation site that is unique to collagen. The galactose and glucose residues are added sequentially by galactosyl and glucosyl transferases. The extent of glycosylation is different in different tissues (Figure-2).
Figure-2- Glycosylation of lysine residue in collagen.
Synthesis of collagen- To be continued in next post
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