collagen

• Collagen


  The most abundant protein in the human body, a major component of the extracellular matrix (ECM) of loose connective tissue, bone, tendons, skin, blood vessel walls, and the sclera and cornea of the eye
• Types of collagen


  • Fibril-forming collagen: Types I, II, III
  • Network-forming collagen: Types IV, VIII
  • Fibril-associated collagen: Types IX, XII
• Type I collagen


  • Found in supporting elements like tendons and cornea
  • Has a rope-like triple helix structure
• Type II collagen


  • Restricted to cartilaginous structures
  • Has a rope-like triple helix structure
• Type III collagen


  • Found in blood vessels
  • Has a rope-like triple helix structure
• Type IV and VIII collagen


  • Form a three-dimensional mesh, type IV constitutes a major part of basement membranes
• Type IX and XII collagen


  • Bind to the surface of collagen fibrils, linking them to one another and to other components in the ECM
• Tropo-collagen


  A triple helical structure that is stabilized by inter-chain hydrogen bonds, formed of three polypeptide chains (called α chains) which wrap around one another into a right-handed super-helix (rope-like)
• Structure of tropo-collagen


  • Each single chain of the triple helix is twisted into a left-handed helix of 3 amino acid residues per turn (Gly–X–Y)
  • The glycine residue is found in every third position as part of a repeating sequence, (Gly–X–Y)
  • X is frequently proline, and Y is often hydroxyproline or hydroxylysine
  • Proline facilitates the formation of the helical conformation of each α chain because its ring structure causes "kinks" in the peptide chain
• Hydroxyproline and hydroxylysine


  Amino acids that result from the hydroxylation of some of the proline and lysine residues after their incorporation into polypeptide chains, an example of post-translational modification
• Collagen contains no tryptophan and cysteine residues in mature collagen
• Collagen structure


  Relates to its function: Tight parallel fibers in tendons provide great tensile strength, arranged at an angle in bone and teeth to resist mechanical shear, loosely woven and flexible in skin, transparent with minimal light scattering in cornea, form gel in vitreous humor of eye
• Collagen biosynthesis


  1. Formation of pro-α chains

  2. Hydroxylation of proline and lysine residues

  3. Glycosylation of some hydroxylysine residues

  4. Assembly and secretion of procollagen

  5. Extracellular cleavage of procollagen molecules

  6. Formation of collagen fibrils

  7. Cross-link formation
• Lysyl oxidase


  Cu2+-containing enzyme that oxidatively deaminates some of the lysine and hydroxylysine residues in collagen, forming allysine and hydroxyallysine that can condense with another lysine or hydroxylysine residues in neighboring collagen molecules to form covalent cross-links and mature collagen fibers
• Normal collagens are highly stable molecules, having half-lives for several years
• Collagen degradation


  Breakdown of collagen fibers is performed by a family of collagenases, into smaller fragments that can be phagocytosed and further degraded by lysosomal enzymes
• Collagen diseases (Collagenopathies)


  • Osteogenesis imperfecta (brittle bone disease)
  • Scurvy
  • Ehlers-Danlos syndrome
• Osteogenesis imperfecta


  A genetic disorder of bone fragility characterized by bones that fracture easily, with minor or no trauma, due to mutations of type I collagen genes that prevent the formation of the triple-helix
• Scurvy


  Vitamin C deficiency leads to a defect in hydroxylation of proline and lysine, resulting in the production of weak and fragile collagen of bone, teeth, gums, skin, capillaries
• Ehlers-Danlos syndrome


  A connective tissue disorder due to defects in collagen, the classic form is characterized by skin extensibility and fragility and joint hypermobility due to defects in type V collagen