Collagen & its Related Disorders
Collagen:
The collagens are a family of fibrous proteins found in all multicellular animals. They
are secreted in large quantities by connective-tissue cells and in smaller quantities by
many other cell types. As a major component of skin and bone, collagens are the most
abundant proteins in mammals, where they constitute 25% of the total protein mass.
The primary feature of a typical collagen molecule is its long, stiff, triplestranded
helical structure, in which three collagen polypeptide chains, called α chains, are
wound around one another in a rope-like superhelix (Figure 19–38). Collagens are
extremely rich in proline and glycine, both of which are important in the formation of
the triple-stranded helix.
Structure of collagen:
(A) A model of part of a single collagen α chain, in which each amino acid is
represented by a sphere. The chain is about 1000 amino acids long. It is arranged as a
left-handed helix, with three amino acids per turn and with glycine as every third
amino acid. Therefore, an α chain is composed of a series of triplet Gly-X-Y
sequences, in which X and Y can be any amino acid (although X is commonly proline
and Y is commonly hydroxyproline, a form of proline that is chemically modified
during collagen synthesis in the cell). (B) A model of part of a collagen molecule, in
which three α chains, each shown in a different color, are wrapped around one another
to form a triple-stranded helical rod. Glycine is the only amino acid small enough to
occupy the crowded interior of the triple helix. Only a short length of the molecule is
shown; the entire molecule is 300 nm long.
Mechanism of collagen synthesis:
Individual collagen polypeptide chains are synthesized on membrane-bound
ribosomes and injected into the lumen of the endoplasmic reticulum (ER) as larger
precursors, called pro-alpha chains. These precursors not only have the short amino-
terminal signal peptide required to direct the nascent polypeptide to the ER but also
have, at both their N- and C-terminal ends, additional amino acids, called pro-
peptides, that are clipped off at a later step of collagen assembly.
, Moreover, in the lumen of the ER, selected prolines and lysines are hydroxylated to
form hydroxyproline (prolyl hydroxylase) and hydroxylysine (lysyl hydroxylase) ,
respectively, and some hydroxylysines are then glycosylated. Each pro-α chain
combines with two others to form a triple-stranded, helical molecule known as pro-
collagen. The hydroxyl groups of hydroxyprolines and hydroxylysines (Figure 19–40)
form inter-chain hydrogen bonds that help stabilize the triple-stranded helix. The
enzyme that catalyzes proline hydroxylation requires ascorbic acid (vitamin C). .
After secretion, the propeptides of the fibrillar procollagen molecules are removed by
specific proteolytic enzymes outside the cell. This converts the pro-collagen
molecules to collagen, which assemble in the extracellular space to form much larger
collagen fibrils. The pro-peptides have at least two functions: First,they guide the
intracellular formation of the triple-stranded collagen molecules. Second, because
they are retained until after secretion, they prevent the intracellular formation of large
collagen fibrils, which could be destructive for the cell.
Now pro-collagen move towards Golgi-complex and it is ready to leave the cell. After
secretion pro-peptides are removed by C- & N-procollagen peptidase to form tropo-
collagen. Now tropo-collagens combine in such a way to form staggered pattern. In
final step, lysyl oxidase (copper-dependent enzyme) that oxidize lysine and
hydroxylysine in collagen and elastin and form covalent cross-linkages, essential
process for connective tissue maturation to form collagen.
Collagen:
The collagens are a family of fibrous proteins found in all multicellular animals. They
are secreted in large quantities by connective-tissue cells and in smaller quantities by
many other cell types. As a major component of skin and bone, collagens are the most
abundant proteins in mammals, where they constitute 25% of the total protein mass.
The primary feature of a typical collagen molecule is its long, stiff, triplestranded
helical structure, in which three collagen polypeptide chains, called α chains, are
wound around one another in a rope-like superhelix (Figure 19–38). Collagens are
extremely rich in proline and glycine, both of which are important in the formation of
the triple-stranded helix.
Structure of collagen:
(A) A model of part of a single collagen α chain, in which each amino acid is
represented by a sphere. The chain is about 1000 amino acids long. It is arranged as a
left-handed helix, with three amino acids per turn and with glycine as every third
amino acid. Therefore, an α chain is composed of a series of triplet Gly-X-Y
sequences, in which X and Y can be any amino acid (although X is commonly proline
and Y is commonly hydroxyproline, a form of proline that is chemically modified
during collagen synthesis in the cell). (B) A model of part of a collagen molecule, in
which three α chains, each shown in a different color, are wrapped around one another
to form a triple-stranded helical rod. Glycine is the only amino acid small enough to
occupy the crowded interior of the triple helix. Only a short length of the molecule is
shown; the entire molecule is 300 nm long.
Mechanism of collagen synthesis:
Individual collagen polypeptide chains are synthesized on membrane-bound
ribosomes and injected into the lumen of the endoplasmic reticulum (ER) as larger
precursors, called pro-alpha chains. These precursors not only have the short amino-
terminal signal peptide required to direct the nascent polypeptide to the ER but also
have, at both their N- and C-terminal ends, additional amino acids, called pro-
peptides, that are clipped off at a later step of collagen assembly.
, Moreover, in the lumen of the ER, selected prolines and lysines are hydroxylated to
form hydroxyproline (prolyl hydroxylase) and hydroxylysine (lysyl hydroxylase) ,
respectively, and some hydroxylysines are then glycosylated. Each pro-α chain
combines with two others to form a triple-stranded, helical molecule known as pro-
collagen. The hydroxyl groups of hydroxyprolines and hydroxylysines (Figure 19–40)
form inter-chain hydrogen bonds that help stabilize the triple-stranded helix. The
enzyme that catalyzes proline hydroxylation requires ascorbic acid (vitamin C). .
After secretion, the propeptides of the fibrillar procollagen molecules are removed by
specific proteolytic enzymes outside the cell. This converts the pro-collagen
molecules to collagen, which assemble in the extracellular space to form much larger
collagen fibrils. The pro-peptides have at least two functions: First,they guide the
intracellular formation of the triple-stranded collagen molecules. Second, because
they are retained until after secretion, they prevent the intracellular formation of large
collagen fibrils, which could be destructive for the cell.
Now pro-collagen move towards Golgi-complex and it is ready to leave the cell. After
secretion pro-peptides are removed by C- & N-procollagen peptidase to form tropo-
collagen. Now tropo-collagens combine in such a way to form staggered pattern. In
final step, lysyl oxidase (copper-dependent enzyme) that oxidize lysine and
hydroxylysine in collagen and elastin and form covalent cross-linkages, essential
process for connective tissue maturation to form collagen.
