Cartilage Oligomeric Matrix Protein (COMP). Functions in collagen binding and assembly

Sammanfattning: Connective tissues contain a prominent extracellular matrix that provides mechanical and physical properties. This extracellular matrix contains as a major constituent a network of collagen fibres. These are composed of collagen fibrils, which in turn are assembled from many collagen molecules aligned parallel to each other. Several proteins, e.g. collagens, leucine-rich repeat proteins and thrombospondins, influence the fibril formation. One of these, COMP (thrombospondin 5) is the focus of this thesis. This protein is primarily found in cartilage and tendon. The main collagens in these tissues are, collagen II and I, respectively. We have shown that the pentameric COMP interacts tightly via the C-terminal globular domains of the subunits with four distinct sites on collagen I and II molecules. By these interactions COMP can join up to five collagen molecules and thereby promote the fibril formation. The fibrils form faster and more efficiently. The mature parts of the fibrils did not contain COMP that apparently acts as a catalyst in the early events. The fibrils are homogenous and have a diameter corresponding to those observed in vivo. Further we show that COMP interacts tightly via the C-terminal globular domains with four sites on collagen IX, localised to the different non-collagenous domains. Collagen IX, in turn, is known to interact with collagen II fibrils. The results presented in this thesis suggest that COMP act as a catalyst organising fibrillar collagen molecule into fibrils. It may also cross-bridge mature fibrils by interacting with collagen IX on their surfaces. These functions of COMP are especially important during remodelling of cartilage or tendon during growth or at injury.