Procollagen assembly

Collagen chains are synthesized as longer precursors, called procollagens, with globular extensions—propeptides of about 200 residues—at both ends. These procollagen polypeptide chains are transported into the lumen of the rough endoplasmic reticulum where they undergo hydroxylation and other chemical modifications before they are assembled into triple chain molecules. The terminal propeptides are essential for proper formation of triple... 

Wilson, R., Lees, J.F. and Bulleid, N.J. (1998) Protein disulfide isomerase acts as a molecular chaperone during the assembly of procollagen. Journal of Biological Chemistry 273, 9637-9643. 

Removal of the N- and C-terminal propeptides from fully folded procollagens occurs only after transport of procollagens across the Golgi stacks and results in collagen molecules that are then able to assemble into fibrils. C-proteinase activity is possessed by members of the tolloid family of zinc metalloproteinases,... 

Three pro-a chains assemble to form a triple helical structure (procollagen), which can now be transferred to the Goigi. Modification of oligosaccharide continues in the Golgi. 

This enzyme [EC 3.4.24.14], also known as procollagen A-proteinase, catalyzes the hydrolysis of the A-propep-tide of the collagen chain a-l(l) at Pro—Gin and of a-2(11) chain at Ala—Gin. As a result, A-terminal propeptides of type I and II collagens are released prior to fibril assembly. However, it does not act on type III procollagen. 

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. 

Lamande SR, Bateman JF Procollagen folding and assembly the role of endoplasmic reticulum enzymes and molecular chaperones. Semin Cell Dev Biol 10 455-464,1999. 

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. 

A procollagen triple helix is assembled in the endoplasmic reticulum helix formation is aided by disulfide bonds between N- and C-terminal propeptides, which align the polypeptide chains. Post-translational modification of procollagen is crucial in allowing for collagen fibril formation. For example, in cells deprived of ascorbate, as in the disease scurvy, the procollagen chains are not hydroxylated sufficiently to form stable triple helices at normal body temperature (hydrox-ylation is through the activity of prolyl hydroxylase, which requires the cofactor ascorbic acid). 

Jan 7) Single amino acid substitutions in procollagen VII affect early stages of assembly of anchoring fibrils. J. Biol. Chem. 280(1) 191—198)... 

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