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... 

Procollagen N-proteinase Ehlers-Danlos syndrome type VII autosomal recessive (MIM 225410)... 

Bonadio, J. and Byers, P.H. (1985) Subtle structural alterations in the chains of type-I procollagen produce osteogenesis imperfecta type-II. Nature 316, 363-366. 

Smith, T., Ferreira, L.R., Herbert, C., Norris, K. and Sauk, J.J. (1995) Hsp47 and cyclophilin B traverse the endoplasmic reticulum with procollagen into pre-golgi intermediate vesicles a role for Hsp47 and cyclophilin B in the export of procollagen from the endoplasmic reticulum. Journal of Biological Chemistry 270,18323-18328. 

Walmsley, A.R., Batten, M.R., Lad, U. and Bulleid, N.J. (1999) Intracellular retention of procollagen within the endoplasmic reticulum is mediated by prolyl 4-hydroxylase. Journal of Biological Chemistry 274, 14884-14892. 

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. 

Winter, A.D. and Page, A.P. (2000) Prolyl 4-hydroxylase is an essential procollagen modifying enzyme required for exoskeleton formation and the maintenance of body shape in the nematode Caenorhabditis elegans. Molecular and Cellular Biology 20, 4084-4093. 

Bonfanti, L., Mironov, A. A. Jr., Martinez-Menarguez, J. A. et al. Procollagen traverses the Golgi stack without leaving the lumen of cisternae evidence for cisternal maturation. Cell 95 993-1003,1998. 

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