Procollagen is the soluble precursor of collagen possibly formed by fibroblasts in the process of collagen synthesis.



While studying collagen synthesized by human skin fibroblasts in culture, Layman et al., found that these cells secreted an unusual collagen into the medium that was more soluble than normal collagen and that, upon denaturation, yielded components larger than a chains. Incubation with pepsin caused a limited digestion that converted this protein into a collagen-like molecule. They suggested that this medium protein was a precursor form of collagen possibly involved in transport 1.


Structural Characteristics

Recent reports that biosynthetic precursors of both al and a 2 chains ("procollagens": "pro al", and "pro a2") may be extracted from embryonic rat 2 and chick 3 calvaria, and may be found in the medium of cultured fibroblasts1 and cultured embryonic-chick tendon cells. The procollagens have been characterized as native al and a2 chains with additional terminal peptide sequences of molecular weight about 1.5-2.0 kDa. Noncovalently assembled chains might be stabilized by formation of disulfide bonds between cysteine residues in these extra peptide sequences. In bone culture preparations pro al contains 5 or 6 half-cystine residues per chain, but little or no cysteine was detected in pro a2, and no evidence for disulfide- bond formation between procollagen chains was obtained 4. In contrast, in preparations of cultured fibroblasts 1 and tendon cells 5, data from molecular sieve chromatography gave evidence for association of procollagen chains. In particular, the results of Dehm et al., raised the possibility that three procollagen chains might be assembled through disulfidebonds5. Procollagen, the triple-stranded precursor of chick embryo skull bone collagen, contains two pro a1 and one pro ß2 chains.Physiologically the NH2-peptides are cut off to give an intermediate called altered procollagen (ALT), and subsequent removal of its COOH-peptides yields collagen.


Mode of Action

In a study, incubation of rat calvaria for short times in the presence of a labeled amino acid revealed the existence of a collagen fraction (procollagen) that functions as a biosynthetic precursor of collagen. Procollagen contains an al-like chain (pre-al) that elutes earlier from cellulose than does rat-bone ?l and has a molecular weight, estimated by acrylamide gel electrophoresis, of 120,000. Furthermore, a time-dependent conversion of pre-al to al was demonstrated by incubation of calvaria for periods varying from 9 to 60 min and by a pulse-chase experiment. Limited cleavage of procollagen with pepsin resulted in a molecule with a chain resembling al in chromatographic properties, molecular weight, and relative hydroxyproline and proline contents. Thus, conversion of procollagen to collagen is likely to occur in vivo by a proteolytic mechanism. The additional peptide sequences in procollagen may serve to initiate chain association in triple-helix formation, to facilitate molecular transport, and to inhibit intracellular fibrogenesis 2.



Defect in Conversion of Procollagen to Collagen in a form of Ehlers-Danlos Syndrome:  Three patients with a form of the Ehlers-Danlos syndrome, a generalized disorder of connective tissue, have detectable amounts of procollagen in extracts of their skin and tendon. The activity of procollagen peptidase, the enzyme that converts procollagen to collagen, is reduced in cultures of fibroblasts. The clinical manifestations of this syndrome may be related to impaired enzymatic conversion of procollagen to collagen. Cultures of skin fibroblasts from these patients have an increased rate of synthesis of collagenous protein (collagen and procollagen), possibly related to the inability of these cells to convert procollagen to collagen 6.



1.     Layman DL, McGoodwin EB, Martin GR (1971). The Nature of the Collagen Synthesized by Cultured Human Fibroblasts. PNAS, 68(2):454-458.

2.     Bellamy G, Bornstein P (1971). Evidence for procollagen, a biosynthetic precursor of collagen. PNAS., 68:1138-1142.

3.     Muller PK, McGoodwin E, Martin GR (1971). Studies on protocollagen: identification of a precursor of proto alpha 1. Biochem. Biophys. Res. Commun., 44:110-116.

4.     Bornstein P, Von Der Mark K, Wyke AW, Ehrlich HP, Monson JM (1972). Characterization of the Pro-a1 Chain of Procollagen. J. Biol. Chem., 247:2808-2813.

5.     Dehm P, Jimenez S A, Olse BR, Prockop DJ (1972). A transport form of collagen from embryonic tendon: electron microscopic demonstration of an NH 2 -terminal extension and evidence suggesting the presence of cystine in the molecule (chick embryo-tropocollagen-gel filtration). PNAS, 69(1):60-64.

6.     Lichtenstein JR, Martin GR, Kohn LD, Byers PH, McKusick VA (1973). Defect in Conversion of Procollagen to Collagen in a Form of Ehlers-Danlos Syndrome. Science, 182(109):298-300.  

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