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From Proteopedia
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Collagen 1bkv.pdb
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Structural highlights
Collagen’s secondary structure is a trimeric three-stranded helix and its tertiary structure is made of left-handed helix structures. It is composed of three which contain a repeated . G is Glycine, X is mostly proline, and Y is mostly hydroxyproline.
Glycine, located at every third position, is essential to the formation of the structure because of its side chain, which is only one hydrogen atom. This allows it to fit into the crowded three-stranded helix. The side chain of glycine interacts with adjacent strands through hydrogen bonding, which helps hold the chains together. Proline and hydroxyproline allow the polypeptide chain to fold into a helix in such a way that three of these chains can be twisted together into a triple helix.
There are made up of three amino acids again with the G-X-Y sequence: Glycine, Arginine, and Phenylalanine. There are three specific binding sites on collagen strands with these specific amino acids that integrins in the extracellular matrix bind onto and identify.
Function
As stated in structural highlights, collagen mainly consists of G-X-Y sequences, and the most prevalent contains Glycine, Proline, and Hydroxyproline. Proline and Hydroxyproline allow the polypeptide chain to fold into a helix in such a way that three of these chains can be twisted together into a triple helix. These three amino acids are crucial in giving rise to the structure of collagen, which allows for the rigidity of each molecule of collagen and allows them to function.
Also stated in structure highlights is that collagen consists of binding sites that allow integrins to bind. These integrins help facilitate the collagen synthesis of the helical structure as well as the interactions between triple helices to form fibrils. The rigidity of each molecule as well as being congregated in order to form fibrils allow collagen to be placed under very high tensile strain, and can be stronger than steel gram by gram. This rigidity allows collagen to be placed under tensile strain.
Disease
Collagen is related to a variety of diseases including osteoporosis, osteogenesis imperfecta, and chondrodysplasias to name a few.
This section will be focusing on corneal degeneration and how bioengineering human donor corneas using high-purity, medical-grade collagen can help restore sight in those who have corneal degenerations.
In corneal degeneration, abnormal material accumulates in the cornea and may lead to corneal blindness. One way to counter this is to have a human corneal transplant, but as these are rare to find, researchers in Linköping University have started to bioengineer versions of human donor corneas to use as transplants for patients with corneal blindness from degeneration of the cornea. These artificially created corneas were made by molds that resulted in the ability to maintain the shape and structure of the human cornea. However, after testing the artificially created cornea, it still did not match the values of the human cornea in tensile strength, elasticity, stiffness, and toughness. Although these bioengineered corneas are not a definitive replacement for the human donor cornea, there have been improvements in the development in a cornea as more research is being done to create one that can match the human donor cornea.
Relevance
Collagen is the most abundant protein found in the human body (~30% of the protein content in the human body consists of collagen). As stated in the function of collagen, they are found in fibrous tissues in the body including ligaments, blood vessels, bones, the cornea, and the skin. This protein is important as it provides high tensile strength as it is packed side by side to create collagen fibers allowing it to withstand enormous forces without being broken. By forming these fibers, it allows the connection between muscle and bone in organisms through the form of tendons. Since these collagen fibers can withstand a lot of stress without breaking, there has been more research focusing on creating collagen-like fibers that can withstand higher stresses.
References
1) Karsdal, M. A., Leeming, D. J., Henriksen, K., & Bay-Jensen, A. (2016). Biochemistry of collagens, laminins and elastin: structure, function and biomarkers. London: Academic Press.
2) Emsley, J., Knight, C., Farndale, R. W., Barnes, M. J., & Liddington, R. C. (2000). Structural Basis of Collagen Recognition by Integrin α2β1. Cell, 101(1), 47-56. doi:10.1016/s0092-8674(00)80622-4
3) Mayne, R., & Burgeson, R. E. (1987). Structure and function of collagen types. Orlando: Academic Press.
4) The Corneal Dystrophy Foundation. (n.d.). What is Corneal Dystrophy? Retrieved February 21, 2018, from https://www.cornealdystrophyfoundation.org/what-is-corneal-dystrophy
5) Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. 4th edition. New York: W. H. Freeman; 2000. Section 22.3, Collagen: The Fibrous Proteins of the Matrix. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21582/
6) Koulikovska M, Rafat M, Petrovski G, et al. Enhanced Regeneration of Corneal Tissue via a Bioengineered Collagen Construct Implanted by a Nondisruptive Surgical Technique. Tissue Eng Part A. 2015;21(5-6): 1116-1130.
