Procollagen self-assembly

Colombo M, Brittingham RJ, Klement JF, Majsterek I, Birk DE, Uitto J, Eertala A (2003) Procollagen VII self-assembly depends on site-specific interactions and is promoted by cleavage of the NC2 domain with procollagen C-proteinase. Biochemistry 42 11434—11442... 

Kadler K, Hojima Y, Prockop DJ (1987) Assembly of collagen fibrils de novo by cleavage of the type I pC-collagen with procollagen C-proteinase. Assay of critical concentration demonstrates that collagen self-assembly is a classical example of an entropy-driven process. J Biol Chem 262 15696-15701... 

Since fibril assembly can be regarded in part as a spontaneous self-assembly process, the limitation of fibril size could be ascribed to a physical equilibrium between soluble procollagen molecules and the growing insoluble fibril. Fibril-forming collagens are synthesized as precursor... 

Figure 5.7. Diagram showing role of N- and C-propeptides in collagen self-assembly. The procollagen molecule is represented by a straight line with bent (N-propeptide) and circular (C-propeptide) regions. Initial linear and lateral aggregation is promoted by the presence of both the N- and C-propeptides. In the presence of both propeptides lateral assembly is limited and the fibrils are narrow. Removal of the N-propeptide results in lateral assembly of narrow fibrils removal of the C-propeptide results in additional lateral growth of fibrils. As indicated in the diagram, the presence of the N- and C-propeptides physically interferes with fibril formation.

Berg RA, Birk DE, Silver FH. Physical characterization of type I procollagen in solution Evidence that the propeptides limit self-assembly, Int J Biol Macromol. 1986 8 177-182. 

The procollagen molecule is secreted from the cell, and the extension propeptides are excised by two specific procollagen peptidases to form the tropocollagen molecule. The removal of the peptides (Mr = 20,000 and 35,000) allows the tropocollagen molecules to self-assemble to form fibrils. This assembly is regulated to some extent by the cells and by other extracellular components to produce the wide variety of structures found in collagen fibers. 

In the extracellular space, procollagen is further modified by enzymes which cut the C- and N-terminal portions of the molecule and make tropocollagen suitable for self-assembly into banded fibrils. The last enzymatic modification of the collagen molecule is by lysyl oxidase, which initiates a series of reactions leading to the formation of stable intermolecular cross-links. As far as lysyl oxidase is concerned, in vivo, this enzyme activity in rat skin does not seem to be significantly affected by excess of vitamin C in the diet on the contrary, lysyl oxidase was inhibited in a concentration-dependent manner in an in vitro assay in which lysyl oxidase activity of chick embryo bones was measured in the presence of increasing concentrations of ascorbic acid (Quaglino et aL, 1991). A similar reduction was also observed by Paris et al. (1984) in cultures of rabbit aortic smooth muscle cells. 

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