Evidence for Procollagen, a Biosynthetic Precursor of Collagen

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 α1-like chain (pre-α1) that elutes earlier from CM-cellulose than does rat-bone α1 and has a molecular weight, estimated by acrylamide gel electrophoresis, of 120,000. A time-dependent conversion of pre-α1 to α1 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 α1 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.