Collagen is a very critical structural protein in many of our connective tissues. Defects in collagen produce diseases such as Ehlers-Danlos syndrome, where there is a defective lysyl hydroxylase gene, or osteogenesis imperfecta, where there is a defect in the production of type I collagen. Which of the following represents the basic repeating tripeptide of collagen?
The basic repeating unit of collagen is Gly-X-Y, where X and Y are proline and lysine.
Collagen is first synthesized in the rough ER as a pre-pro-collagen alpha chain composed mainly of a repeating tripeptide of the sequence Gly-X-Y. A hydrophobic sequence is cleaved producing the pro-collagen alpha chain. The pro-collagen alpha chain is then hydryoxylated on the prolines (X) and lysines (Y). The alpha chain is then glycosylated and three alpha chains then form a trimer. The trimer is exocytosed, and the ends are cleaved, leaving behind the insoluble tropocollagen. The lysyl oxidase then covalently crosslinks the tropocollagens by the hydroxylysines to produce collagen fibrils. Finally, the fibrils aggregate to form the final bundles of collagen.
Lodish et al. review collagen. Collagen type I was the first to be isolated; one unit is 300 nm in length and 1.5 nm in diameter, consisting of two alpha 1 chains and one alpha 2 chain. Each chain consists of 1,050 amino acids. The collagen unit adopts a right-handed triple helix formation.
Steiner et al. review the type I collagen disease of osteogenesis imperfecta (OI). OI is characterized by fractures with minimal trauma, hearing loss, skeletal deformities, grey to brown teeth that appear translucent and wear easily, and blue/grey sclera. OI is caused by mutations in the COL1A1 and COL1A2 genes. Testing consists of culturing dermal fibroblasts from a skin biopsy.
Illustration A summarizes the structure of collagen.