Skin fibroblasts from a patient with a lethal form of osteogenesis imperfecta were found to synthesize equal amounts of normal pro-α1(I) chains and pro-α1(I) chains which are about 10% shorter because of a deletion of about 100 amino acids in the middle of the α chain domain. The pro-α1(I) chains were incorporated into three different kinds of trimers: a normal type I trimer with normal length pro-α1(I) chains; a type I(s) trimer with one shortened pro-α1(I) chain and two normal length chains; and a type I(ss) trimer containing two shortened pro-α1(I) chains and one normal length pro-α2(I) chain. As judged by resistance to digestion by chymotrypsin and trypsin, the type I(s) and I(ss) trimers denatured at a temperature at least 3°C lower than normal type I procollagen. Procollagen containing the shortened pro-α1(I) chains was slowly secreted by the cells but was degraded by extracellular proteinases within 6 h of chase into the medium. The results indicated that the presence of the shortened pro-α1(I) chains in procollagen trimers produces a delay in rate of helix formation, overmodification of the polypeptides by post-translational enzymes, a decrease in the thermal stability of the trimers, and increased susceptibility of the protein to endogenous proteinases. Additionally, the fibroblasts of this patient synthesized and secreted a type III-like species of procollagen with unusual chromatographic properties.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Biological Chemistry|
|State||Published - Jan 1 1983|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology