Types I, II, and III collagens are known as fibril-forming collagens. These collagens have a rope-like structure and can be seen as linear polymers of fibrils under an electron microscope. The banding patterns in these fibrils reflect the regular packing of individual collagen molecules. Type I collagen fibers are found in strong supporting elements like tendons and corneas, while type II collagen fibers are restricted to cartilaginous structures. Type III collagen fibers are prevalent in more flexible tissues such as blood vessels.

On the other hand, types IV and VIII collagens are network-forming collagens. Instead of distinct fibrils, they form a three-dimensional mesh. Type IV collagen molecules assemble into a sheet or meshwork, which is a major component of basement membranes. Basement membranes are thin structures that provide mechanical support to adjacent cells and act as a semipermeable filtration barrier in organs like the kidney and lung.

Types IX and XII collagens are fibril-associated collagens. They bind to the surface of collagen fibrils, connecting these fibrils to each other and to other components in the extracellular matrix (ECM).

In terms of structure, collagen differs from globular proteins. It has an elongated, triple-helical structure stabilized by interchain hydrogen bonds. Unlike most proteins, collagen is not folded into compact structures.

Collagen is rich in proline and glycine, both of which play important roles in the formation of the triple-stranded helix. Proline helps in creating the helical conformation of each α chain due to its ring structure causing "kinks" in the peptide chain. Glycine, the smallest amino acid, is found in every third position of the polypeptide chain and fits into the restricted spaces where the three chains of the helix come together. The sequence of the α chain can be represented as (−Gly–Pro–Hyp–)333, with Hyp often being hydroxyproline and X frequently being proline.

Collagen contains nonstandard amino acids called hydroxyproline and hydroxylysine. These amino acids result from the hydroxylation of proline and lysine residues after their incorporation into polypeptide chains. This hydroxylation is a posttranslational modification that maximizes the formation of interchain hydrogen bonds, stabilizing the triple-helical structure. Additionally, the hydroxyl group of hydroxylysine residues may undergo enzymatic glycosylation, with glucose and galactose being commonly attached to the polypeptide chain prior to triple-helix formation.

The biosynthesis of collagen involves the synthesis of polypeptide precursors in fibroblasts, osteoblasts (in bone), and chondroblasts (in cartilage). These precursors undergo enzymic modifications and form the triple helix, which is then secreted into the ECM. Further enzymic modifications occur, and the mature extracellular collagen fibrils aggregate and become cross-linked, ultimately forming collagen fibers.
Fibril-forming collagens: Types I, II, and III are the fibrillar collagens and have the rope-like structure described above for a typical collagen molecule. In the electron microscope, these linear polymers of fibrils have characteristic banding patterns, reflecting the regular staggered packing of the individual collagen molecules in the fibril (Fig. 4.3). Type I collagen fibers (composed of collagen fibrils) are found in supporting elements of high tensile strength (for example, tendons and corneas), whereas fibers formed from type II collagen molecules are restricted to cartilaginous structures. The fibers derived from type III collagen are prevalent in more distensible tissues such as blood vessels.
2.
Network-forming collagens: Types IV and VIII form a three-dimensional mesh, rather than distinct fibrils (Fig. 4.4). For example, type IV molecules assemble into a sheet or meshwork that constitutes a major part of basement membranes.
Basement membranes are thin, sheet-like structures that provide mechanical support for adjacent cells and function as a semipermeable filtration barrier to macromolecules in organs such as the kidney and the lung.
3. Fibril-associated collagens: Types IX and XII bind to the surface of collagen fibrils, linking these fibrils to one another and to other components in the ECM (see Fig. 4.2).
B. Structure
Unlike most globular proteins that are folded into compact structures, collagen, a fibrous protein, has an elongated, triple-helical structure that is stabilized by interchain hydrogen bonds.
1.
Amino acid sequence: Collagen is rich in proline and glycine, both of which are important in the formation of the triple-stranded helix. Proline facilitates the formation of the helical conformation of each α chain because its ring structure causes “kinks” in the peptide chain. [Note: The presence of proline dictates that the helical conformation of the α chain cannot be an α helix (see p. 16).] Glycine, the smallest amino acid, is found in every third position of the polypeptide chain. It fits into the restricted spaces where the three chains of the helix come together. The glycine residues are part of a repeating sequence, −Gly–X–Y–, where X is frequently proline, and Y is often hydroxyproline (but can be hydroxylysine, Fig. 4.5). Thus, most of the α chain can be regarded as a polytripeptide whose sequence can be represented as (−Gly–Pro– Hyp–)333.
2.
Hydroxyproline and hydroxylysine: Collagen contains hydroxyproline and hydroxylysine, which are nonstandard amino acids (see p. 1) not present in most other proteins. They result from the hydroxylation of some of the proline and lysine residues after their incorporation into polypeptide chains (Fig. 4.6). Therefore, the hydroxylation is a posttranslational modification (see p. 460). [Note: Generation of hydroxyproline maximizes formation of interchain hydrogen bonds that stabilize the triple-helical structure.] 3. Glycosylation: The hydroxyl group of the hydroxylysine residues of collagen may be enzymatically glycosylated. Most commonly, glucose and galactose are sequentially attached to the polypeptide chain prior to triple-helix formation (Fig. 4.7).
C. Biosynthesis
The polypeptide precursors of the collagen molecule are synthesized in fibroblasts (or in the related osteoblasts of bone and chondroblasts of cartilage). They are enzymically modified and form the triple helix, which gets secreted into the ECM. After additional enzymic modification, the mature extracellular collagen fibrils aggregate and become cross-linked to form collagen fibers.
1.