Collagen procollagen

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... 

Many other peptides are synthesized as proproteins that require modifications before attaining biologic activity. Many of the posttranslational modifications involve the removal of amino terminal amino acid residues by specific aminopeptidases. Collagen, an abundant protein in the extracellular spaces of higher eukaryotes, is synthesized as procollagen. Three procol-... 

A number of iron-containing, ascorbate-requiring hydroxylases share a common reaction mechanism in which hydroxylation of the substrate is linked to decarboxylation of a-ketoglutarate (Figure 28-11). Many of these enzymes are involved in the modification of precursor proteins. Proline and lysine hydroxylases are required for the postsynthetic modification of procollagen to collagen, and prohne hydroxylase is also required in formation of osteocalcin and the Clq component of complement. Aspartate P-hydroxylase is required for the postsynthetic modification of the precursor of protein C, the vitamin K-dependent protease which hydrolyzes activated factor V in the blood clotting cascade. TrimethyUysine and y-butyrobetaine hydroxylases are required for the synthesis of carnitine. 

The same ceUs that secrete collagen also secrete fi-bronectin, a large glycoprotein present on cell surfaces, in the extracellular matrix, and in blood (see below). Fi-bronectin binds to aggregating precollagen fibers and alters the kinetics of fiber formation in the pericellular matrix. Associated with fibronectin and procollagen in... 

Type I collagen molecules are heterotrimeric molecules with an a chain composition of two al (I) chains and one o 2(I) chain from the COLlAl and COLl A2 genes, respectively. This a chain composition is written as [a 1(1)] 20 2 (I). A type I collagen molecule is synthesized as a procollagen type I molecule. The N- and C-terminal propeptides are cleaved as part of the processing in tissues and are called N- and C-propeptides, respectively. The human pro-o (I) and pro-o 2(I) have 246 and 247 residues in their C-propeptides, respectively. The C-propeptide contains interchain disulfide bonds, which are important for the stabilization of the three a chains in the endoplasmic reticulum (ER). 

Processing of a newly synthesized type V procollagen molecule is also different from that of type I collagen. BMP-1, which is the C-propeptidase of type I, II, and III collagens, cleaves the N-terminal propeptide of the pro-al(V) chain, and a furin-like proteinase cleaves the C-terminal propeptide. The tyrosine residue in the N-terminal NC domain of type V collagen is sulfated. This modification might be related to... 

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