COLLAGEN - A NOT SO SIMPLE PROTEIN

Collagen is the major protein of animal bodies from simple sponges to Homo sapiens and exists in various forms from skin, tendon and bone to cornea and basement membrane of the capillaries. This biological vari ation can now be accounted for on the basis of a whole family of genet ically distinct collagens. Over the past two decades 19 different coll agens have been identified, although the major types are the fibrous t ypes I, II and III and the non-fibrous type IV of basement membrane. T hey all possess the basic triple helix based on multiple repeals of th e simple tri-peptide Gly-X-Y, but this varies in length and forms diff erent supramolecular aggregates to achieve optimum function for partic ular tissues. The major function of collagen is to provide shape and m echanical strength and the latter is achieved by intermolecular crossl inking of the collagen molecules in the supramolecular aggregate. The monomeric molecules in the aggregates are stabilised by two different pathways. Initially cross-linking occurs through an enzymic mechanism involving oxidation of specific lysine and hydroxylysine residues prov iding divalent crosslinking which subsequently matures to multivalent cross-links. As the rate of turnover decreases a nonenzymic pathway ta kes over, which is mediated through the adventitious accretion of gluc ose. Collagen therefore, unlike other proteins shows considerable chan ges with age which in turn affect its physical properties. These chang es must be taken into account when preparing collagen based products. All the amino acid side chains project radially from the rod-like trip le helix and the quarter-staggered array of the molecules allows highl y specific intermolecular cross-linking either naturally, or artificia lly with bifunctional reagents. Reactions with basic or acid groups ca n therefore be carefully controlled and in some cases their location p redicted. Synthetic cross-links bind the molecules closer together and increase intermolecular interactions, thus increasing the shrinkage t emperature and resistance to enzymic degradation. The turnover of coll agen is generally slow but in fact can vary from 2/3 days for periodon tal ligament to several years for skin and tendon. Mature collagen fib res are highly resistant to enzymes and degradation is achieved by spe cific collagenase that can cleave the triple helix at one particular p oint. The shorter helical fragments can then unravel and denature to g elatin when other metalloproteinases (MMPs) degrade it to amino acids. A family of 14 metalloproteinases have been identified along with som e specific tissue inhibitors (TIMPS). The sharp denaturation temperatu re of collagen attests to the almost crystalline character of the trip le helix and the variation in shrinkage temperature between species is primarily due to the number of hydroxyproline based water hydrogen br idges. The presence of a hydroxyproline deficient thermally labile dom ain near the carboxy terminus of the molecule initiates the melting pr ocess allowing the triple helix to unzip along its length. Recent stud ies have demonstrated that collagen is not an inert structural materia l but interacts with other molecules to control the development of col lagenous tissues. Despite the ancient lineage of this ubiquitous prote in, collagen is still revealing exciting new scientific features.