Enzymes converting procollagens to collagens

Abstract

Conversion from procollagen to collagen is a specific process that is a requirement for proper alignment of collagen molecules to form functional fibers. This process is catalyzed by at least three structurally and functionally distinct enzymes cleaving collagen types I-III. The cleavage processes possibly taking place in the more recently discovered collagen types are not known to any extent at this time. Two amino-terminal proteinases, one cleaving type I and type II procollagens and the other cleaving type III procollagen, have been purified close to homogeneity, and the more unspecific activity of carboxy-terminal proteinase has been isolated from several tissues. In our experimental model, however, cleavage of the carboxy-terminal propeptides of types I and III procollagen is differently affected by lysine. This suggests the presence of at least two distinct enzymes for the removal of carboxyl-terminal propeptides. The regulation of the reaction process from procollagen to collagen is not well known at present. The importance of the phenomenon in terms of fibril formation, however, is demonstrated by several elegant studies in vitro; and certain genetic disorders in which this process is defective demonstrate the significance in vivo. Moreover, the factors shown to effect the cleavage process may be potentially beneficial in the treatment of the pathological processes with abnormal collagen accumulation such as fibrosis. In this paper we briefly review the current knowledge of the converting enzymes, including some very recent findings of our laboratory as well as the evidence presented for the biological significance of the conversion process.

Type I Collagen in Hsp47-null Cells Is Aggregated in Endoplasmic Reticulum and Deficient in N-Propeptide Processing and Fibrillogenesis

“…In contrast, C-propeptide cleavage, which is essential for the fibril formation (Peltonen et al, 1985), occurred normally in Hsp47 Ϫ/Ϫ cells. Consistently, C-propeptide cleavage was reported to occur even though the triple helix of procollagen was destabilized by mutation (Vogel et al, 1987(Vogel et al, , 1988.…”

Regulation of procollagen amino-propeptide processing during mouse embryogenesis by specialization of homologous ADAMTS proteases: insights on collagen biosynthesis and dermatosparaxis

“…The results suggest that ADAMTS2 is the major procollagen III amino-propeptidase in mice, but that it appears to share the procollagen I processing function with ADAMTS3. Previous literature had suggested that a significant proportion of procollagen III in tissues was unprocessed and that the procollagen III-processing enzyme was not the same enzyme that processed procollagen I Peltonen et al, 1985;Tuderman and Prockop, 1982). Wang et al recently demonstrated that ADAMTS2 could process procollagen III in vitro, but the in vivo relevance was unclear (Wang et al, 2003).…”

Evidence for altered synthesis of type II collagen in patients with osteoarthritis.

“…The procollagen molecule is secreted from the cell into the extracellular matrix where it forms fibrils. This is accompanied by the removal of the C-and N-propeptides, by specific C-and N-proteinases, as collagen fibrils are formed (7).…”